@article{%a1.%Y,

title = {Desmin and Plectin Recruitment to the Nucleus and Nuclei Orientation Are Lost in Emery-Dreifuss Muscular Dystrophy Myoblasts Subjected to Mechanical Stimulation},

author = {Cenni V and Evangelisti C and Santi S and Sabatelli P and Neri S and Cavallo M and Lattanzi G and Mattioli E},

url = {https://www.mdpi.com/2073-4409/13/2/162},

doi = {10.3390/cells13020162},

year  = {2024},

date = {2024-01-31},

journal = {Cells},

volume = {13},

issue = {2},

pages = {162},

abstract = {n muscle cells subjected to mechanical stimulation, LINC complex and cytoskeletal proteins are basic to preserve cellular architecture and maintain nuclei orientation and positioning. In this context, the role of lamin A/C remains mostly elusive. This study demonstrates that in human myoblasts subjected to mechanical stretching, lamin A/C recruits desmin and plectin to the nuclear periphery, allowing a proper spatial orientation of the nuclei. Interestingly, in Emery-Dreifuss Muscular Dystrophy (EDMD2) myoblasts exposed to mechanical stretching, the recruitment of desmin and plectin to the nucleus and nuclear orientation were impaired, suggesting that a functional lamin A/C is crucial for the response to mechanical strain. While describing a new mechanism of action headed by lamin A/C, these findings show a structural alteration that could be involved in the onset of the muscle defects observed in muscular laminopathies.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1.%Y_126,

title = {Clinical and functional characterization of COL2A1 p.Gly444Ser variant: From a fetal phenotype to a previously undisclosed postnatal phenotype},

author = {Marchionni E and D'Apice MR and Lupo V and Lattanzi G and Mattioli E and Lisignoli G and Gabusi E and Pepe G and Helmer Citterich M and Campione E and Nardone AM and Spitalieri P and Pucci N and Cocciadiferro D and Picchi E and Garaci F and Novelli A and Novelli G.},

url = {https://www.sciencedirect.com/science/article/pii/S2352187223000748?via%3Dihub},

doi = {10.1016/j.bonr.2023.101728},

year  = {2023},

date = {2023-02-23},

journal = {Bone reports},

volume = {19},

pages = {101728},

abstract = {COL2A1 gene encodes the alpha-1 chain of type-II procollagen. Heterozygous pathogenic variants are associated with the broad clinical spectrum of genetic diseases known as type-II collagenopathies. We aimed to characterize the NM_001844.5:c.1330G>A;p.Gly444Ser variant detected in the COL2A1 gene through trio-based prenatal exome sequencing in a fetus presenting a severe skeletal phenotype at 31 Gestational Weeks and in his previously undisclosed mild-affected father. Functional studies on father's cutaneous fibroblasts, along with in silico protein modeling and in vitro chondrocytes differentiation, showed intracellular accumulation of collagen-II, its localization in external Golgi vesicles and nuclear morphological alterations. Extracellular matrix showed a disorganized fibronectin network. These results showed that p.Gly444Ser variant alters procollagen molecules processing and the assembly of mature type-II collagen fibrils, according to COL2A1-chain disorganization, displayed by protein modeling. Clinical assessment at 38 y.o., through a reverse-phenotyping approach, revealed limp gait, short and stocky appearance. X-Ray and MRI showed pelvis asymmetry with severe morpho-structural alterations of the femoral heads bilaterally, consistent with a mild form of type-II collagenopathy. This study shows how the fusion of genomics and clinical expertise can drive a diagnosis supported by cellular and bioinformatics studies to effectively establish variants pathogenicity.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1.%Y_132,

title = {Mineralocorticoid Receptor Antagonism Prevents Type 2 Familial Partial Lipodystrophy Brown Adipocyte Dysfunction},

author = {Schena E and Mattioli E and Peres C and Zanotti L and Morselli P and Iozzo P and Guzzardi MA and Bernardini C and Forni M and Nesci S and Caprio M and Cecchetti C and Pagotto U and Gabusi E and Cattini L and Lisignoli G and Blalock WL and Gambineri A and Lattanzi G},

url = {https://www.mdpi.com/2073-4409/12/22/2586},

doi = {10.3390/cells12222586},

year  = {2023},

date = {2023-10-10},

urldate = {2023-10-10},

journal = {CELLS},

volume = {12},

issue = {22},

pages = {2586},

abstract = {Type-2 Familial Partial Lipodystrophy (FPLD2), a rare lipodystrophy caused by LMNA mutations, is characterized by a loss of subcutaneous fat from the trunk and limbs and excess accumulation of adipose tissue in the neck and face. Several studies have reported that the mineralocorticoid receptor (MR) plays an essential role in adipose tissue differentiation and functionality. We previously showed that brown preadipocytes isolated from a FPLD2 patient's neck aberrantly differentiate towards the white lineage. As this condition may be related to MR activation, we suspected altered MR dynamics in FPLD2. Despite cytoplasmic MR localization in control brown adipocytes, retention of MR was observed in FPLD2 brown adipocyte nuclei. Moreover, overexpression of wild-type or mutated prelamin A caused GFP-MR recruitment to the nuclear envelope in HEK293 cells, while drug-induced prelamin A co-localized with endogenous MR in human preadipocytes. Based on in silico analysis and in situ protein ligation assays, we could suggest an interaction between prelamin A and MR, which appears to be inhibited by mineralocorticoid receptor antagonism. Importantly, the MR antagonist spironolactone redirected FPLD2 preadipocyte differentiation towards the brown lineage, avoiding the formation of enlarged and dysmorphic lipid droplets. Finally, beneficial effects on brown adipose tissue activity were observed in an FPLD2 patient undergoing spironolactone treatment. These findings identify MR as a new lamin A interactor and a new player in lamin A-linked lipodystrophies.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1.%Yb_31,

title = {A Single mtDNA Deletion in Association with a LMNA Gene New Frameshift Variant: A Case Report},

author = {Montano V and Mancuso M and Simoncini C and Torri F and Chico L and Ali G and Rocchi A and Baldinotti F and Caligo MA and Lattanzi G and Mattioli E and Cenacchi G and Barison A and Siciliano G and Ricci G},

url = {https://content.iospress.com/articles/journal-of-neuromuscular-diseases/jnd220802},

doi = {10.3233/JND-220802},

year  = {2022},

date = {2022-08-25},

journal = {Journal of neuromuscular diseases},

volume = {9},

issue = {3457-462},

abstract = {Background: Proximal muscle weakness may be the presenting clinical feature of different types of myopathies, including limb girdle muscular dystrophy and primary mitochondrial myopathy. LGMD1B is caused by LMNA mutation. It is characterized by progressive weakness and wasting leading to proximal weakness, cardiomyopathy, and hearth conduction block. Objective: In this article, we describe the case of a patient who presented with limb-girdle weakness and a double trouble scenario -mitochondrial DNA single deletion and a new LMNA mutation. Methods: Pathophysiological aspects were investigated with muscle biopsy, Western Blot analysis, NGS nuclear and mtDNA analysis and neuromuscular imaging (muscle and cardiac MRI). Results: Although secondary mitochondrial involvement is possible, a "double trouble" syndrome can not be excluded. Conclusion: Implication deriving from hypothetical coexistence of two different pathological conditions or the possible secondary mitochondrial involvement are discussed.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1.%Yb_44,

title = {The role of prelamin A post-translational maturation in stress response and 53BP1 recruitment},

author = {Capanni C and Schena E and Di Giampietro ML and Montecucco A and Mattioli E and Lattanzi G},

url = {https://www.frontiersin.org/articles/10.3389/fcell.2022.1018102/full},

doi = {10.3389/fcell.2022.1018102},

year  = {2022},

date = {2022-03-31},

journal = {Frontiers in cell and developmental biology},

volume = {10},

abstract = {Lamin A is a main constituent of the nuclear lamina and contributes to nuclear shaping, mechano-signaling transduction and gene regulation, thus affecting major cellular processes such as cell cycle progression and entry into senescence, cellular differentiation and stress response. The role of lamin A in stress response is particularly intriguing, yet not fully elucidated, and involves prelamin A post-translational processing. Here, we propose prelamin A as the tool that allows lamin A plasticity during oxidative stress response and permits timely 53BP1 recruitment to DNA damage foci. We show that while PCNA ubiquitination, p21 decrease and H2AX phosphorylation occur soon after stress induction in the absence of prelamin A, accumulation of non-farnesylated prelamin A follows and triggers recruitment of 53BP1 to lamin A/C complexes. Then, the following prelamin A processing steps causing transient accumulation of farnesylated prelamin A and maturation to lamin A reduce lamin A affinity for 53BP1 and favor its release and localization to DNA damage sites. Consistent with these observations, accumulation of prelamin A forms in cells under basal conditions impairs histone H2AX phosphorylation, PCNA ubiquitination and p21 degradation, thus affecting the early stages of stress response. As a whole, our results are consistent with a physiological function of prelamin A modulation during stress response aimed at timely recruitment/release of 53BP1 and other molecules required for DNA damage repair. In this context, it becomes more obvious how farnesylated prelamin A accumulation to toxic levels alters timing of DNA damage signaling and 53BP1 recruitment, thus contributing to cellular senescence and accelerated organismal aging as observed in progeroid laminopathies.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y__504,

title = {Interleukin-6 neutralization ameliorates symptoms in prematurely aged mice.},

author = {Squarzoni S and Schena E and Sabatelli P and Mattioli E and Capanni C and Cenni V and D'Apice MR and Andrenacci D and Sarli G and Pellegrino V and Festa A and Baruffaldi F and

Storci G and Bonafè M and Barboni C and Sanapo M and Zaghini A and Lattanzi G},

url = {https://onlinelibrary.wiley.com/doi/10.1111/acel.13285},

doi = {10.1111/acel.13285},

year  = {2021},

date = {2021-03-09},

urldate = {2021-03-09},

journal = {Aging Cell},

volume = {20},

number = {1},

pages = {e13285},

abstract = {Hutchinson-Gilford progeria syndrome (HGPS) causes premature aging in children, with adipose tissue, skin and bone deterioration, and cardiovascular impairment. In HGPS cells and mouse models, high levels of interleukin-6, an inflammatory cytokine linked to aging processes, have been detected. Here, we show that inhibition of interleukin-6 activity by tocilizumab, a neutralizing antibody raised against interleukin-6 receptors, counteracts progeroid features in both HGPS fibroblasts and LmnaG609G / G609G progeroid mice. Tocilizumab treatment limits the accumulation of progerin, the toxic protein produced in HGPS cells, rescues nuclear envelope and chromatin abnormalities, and attenuates the hyperactivated DNA damage response. In vivo administration of tocilizumab reduces aortic lesions and adipose tissue dystrophy, delays the onset of lipodystrophy and kyphosis, avoids motor impairment, and preserves a good quality of life in progeroid mice. This work identifies tocilizumab as a valuable tool in HGPS therapy and, speculatively, in the treatment of a variety of aging-related disorders.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_436,

title = {Emerin Phosphorylation during the Early Phase of the Oxidative Stress Response Influences Emerin-BAF Interaction and BAF Nuclear Localization},

author = {Cenni V and Squarzoni S and Loi M and Mattioli E and Lattanzi G and Capanni C},

url = {https://www.mdpi.com/2073-4409/9/6/1415},

doi = {10.3390/cells9061415},

year  = {2020},

date = {2020-01-01},

urldate = {2020-01-01},

journal = {Cells},

volume = {9},

number = {6},

pages = {1415},

abstract = {Reactive Oxygen Species (ROS) are reactive molecules required for the maintenance of physiological functions. Oxidative stress arises when ROS production exceeds the cellular ability to eliminate such molecules. In this study, we showed that oxidative stress induces post-translational modification of the inner nuclear membrane protein emerin. In particular, emerin is phosphorylated at the early stages of the oxidative stress response, while protein phosphorylation is abolished upon recovery from stress. A finely tuned balance between emerin phosphorylation and O-GlcNAcylation seems to govern this dynamic and modulates emerin-BAF interaction and BAF nucleoplasmic localization during the oxidative stress response. Interestingly, emerin post-translational modifications, similar to those observed during the stress response, are detected in cells bearing LMNA gene mutations and are characterized by a free radical generating environment. On the other hand, under oxidative stress conditions, a delay in DNA damage repair and cell cycle progression is found in cells from Emery-Dreifuss Muscular Dystrophy type 1, which do not express emerin. These results suggest a role of the emerin-BAF protein platform in the DNA damage response aimed at counteracting the detrimental effects of elevated levels of ROS.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_449,

title = {Lamin A and Prelamin A Counteract Migration of Osteosarcoma Cells},

author = {Evangelisti C and Paganelli F and Giuntini G and Mattioli E and Cappellini A and Ramazzotti G and Faenza I and Maltarello MC and Martelli AM and Scotlandi K and Chiarini F and Lattanzi G},

url = {https://www.mdpi.com/2073-4409/9/3/774},

doi = {10.3390/cells9030774},

year  = {2020},

date = {2020-01-01},

journal = {Cells},

volume = {9},

number = {3},

pages = {774},

abstract = {A type lamins are fundamental components of the nuclear lamina. Changes in lamin A expression correlate with malignant transformation in several cancers. However, the role of lamin A has not been explored in osteosarcoma (OS). Here, we wanted to investigate the role of lamin A in normal osteoblasts (OBs) and OS cells. Thus, we studied the expression of lamin A/C in OS cells compared to OBs and evaluated the effects of lamin A overexpression in OS cell lines. We show that, while lamin A expression increases during osteoblast differentiation, all examined OS cell lines express lower lamin A levels relative to differentiated OBs. The condition of low LMNA expression confers to OS cells a significant increase in migration potential, while overexpression of lamin A reduces migration ability of OS cells. Moreover, overexpression of unprocessable prelamin A also reduces cell migration. In agreement with the latter finding, OS cells which accumulate the highest prelamin A levels upon inhibition of lamin A maturation by statins, had significantly reduced migration ability. Importantly, OS cells subjected to statin treatment underwent apoptotic cell death in a RAS-independent, lamin A-dependent manner. Our results show that pro-apoptotic effects of statins and statin inhibitory effect on OS cell migration are comparable to those obtained by prelamin A accumulation and further suggest that modulation of lamin A expression and post-translational processing can be a tool to decrease migration potential in OS cells.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_435,

title = {Lamin A Involvement in Ageing Processes},

author = {Cenni V and Capanni C and Mattioli E and Schena E and Squarzoni S and Bacalini MG and Garagnani P and Salvioli S and Franceschi C and Lattanzi G},

url = {https://www.sciencedirect.com/science/article/pii/S1568163719302107},

doi = {10.1016/j.arr.2020.101073},

year  = {2020},

date = {2020-01-01},

urldate = {2020-01-01},

journal = {Ageing research reviews},

volume = {62},

pages = {101073},

abstract = {Lamin A, a main constituent of the nuclear lamina, is the major splicing product of the LMNA gene, which also encodes lamin C, lamin A delta 10 and lamin C2. Involvement of lamin A in the ageing process became clear after the discovery that a group of progeroid syndromes, currently referred to as progeroid laminopathies, are caused by mutations in LMNA gene. Progeroid laminopathies include Hutchinson-Gilford Progeria, Mandibuloacral Dysplasia, Atypical Progeria and atypical-Werner syndrome, disabling and life-threatening diseases with accelerated ageing, bone resorption, lipodystrophy, skin abnormalities and cardiovascular disorders. Defects in lamin A post-translational maturation occur in progeroid syndromes and accumulated prelamin A affects ageing-related processes, such as mTOR signaling, epigenetic modifications, stress response, inflammation, microRNA activation and mechanosignaling. In this review, we briefly describe the role of these pathways in physiological ageing and go in deep into lamin A-dependent mechanisms that accelerate the ageing process. Finally, we propose that lamin A acts as a sensor of cell intrinsic and environmental stress through transient prelamin A accumulation, which triggers stress response mechanisms. Exacerbation of lamin A sensor activity due to stably elevated prelamin A levels contributes to the onset of a permanent stress response condition, which triggers accelerated ageing.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_147,

title = {Network assessment of demethylation treatment in melanoma: Differential transcriptome-methylome and antigen profile signatures.},

author = {Jiang Z and Cinti C and Taranta M and Mattioli E and Schena E and Singh S and Khurana R and Lattanzi G and Tsinoremas NF and Capobianco E},

url = {https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0206686},

doi = {10.1371/journal.pone.0206686},

year  = {2020},

date = {2020-05-14},

journal = {Plos One},

volume = {13},

number = {11},

pages = {e0206686},

abstract = {BACKGROUND: In melanoma, like in other cancers, both genetic alterations and epigenetic underlie the metastatic process. These effects are usually measured by changes in both methylome and transcriptome profiles, whose cross-correlation remains uncertain. We aimed to assess at systems scale the significance of epigenetic treatment in melanoma cells with different metastatic potential. METHODS AND FINDINGS: Treatment by DAC demethylation with 5-Aza-2'-deoxycytidine of two melanoma cell lines endowed with different metastatic potential, SKMEL-2 and HS294T, was performed and high-throughput coupled RNA-Seq and RRBS-Seq experiments delivered differential profiles (DiP) of both transcriptomes and methylomes. Methylation levels measured at both TSS and gene body were studied to inspect correlated patterns with wide-spectrum transcript abundance levels quantified in both protein coding and non-coding RNA (ncRNA) regions. The DiP were then mapped onto standard bio-annotation sources (pathways, biological processes) and network configurations were obtained. The prioritized associations for target identification purposes were expected to elucidate the reprogramming dynamics induced by the epigenetic therapy. The interactomic connectivity maps of each cell line were formed to support the analysis of epigenetically re-activated genes. i.e. those supposedly silenced by melanoma. In particular, modular protein interaction networks (PIN) were used, evidencing a limited number of shared annotations, with an example being MAPK13 (cascade of cellular responses evoked by extracellular stimuli). This gene is also a target associated to the PANDAR ncRNA, therapeutically relevant because of its aberrant expression observed in various cancers. Overall, the non-metastatic SKMEL-2 map reveals post-treatment re-activation of a richer pathway landscape, involving cadherins and integrins as signatures of cell adhesion and proliferation. Relatively more lncRNAs were also annotated, indicating more complex regulation patterns in view of target identification. Finally, the antigen maps matched to DiP display other differential signatures with respect to the metastatic potential of the cell lines. In particular, as demethylated melanomas show connected targets that grow with the increased metastatic potential, also the potential target actionability seems to depend to some degree on the metastatic state. However, caution is required when assessing the direct influence of re-activated genes over the identified targets. In light of the stronger treatment effects observed in non-metastatic conditions, some limitations likely refer to in silico data integration tools and resources available for the analysis of tumor antigens. CONCLUSION: Demethylation treatment strongly affects early melanoma progression by re-activating many genes. This evidence suggests that the efficacy of this type of therapeutic intervention is potentially high at the pre-metastatic stages. The biomarkers that can be assessed through antigens seem informative depending on the metastatic conditions, and networks help to elucidate the assessment of possible targets actionability.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_475,

title = {PCAF Involvement in Lamin A/C-HDAC2 Interplay during the Early Phase of Muscle Differentiation},

author = {Santi S and Cenni V and Capanni C and Lattanzi G and Mattioli E},

url = {https://www.mdpi.com/2073-4409/9/7/1735},

doi = {10.3390/cells9071735},

year  = {2020},

date = {2020-01-01},

urldate = {2020-01-01},

journal = {Cells},

volume = {9},

number = {7},

pages = {E1735},

abstract = {Lamin A/C has been implicated in the epigenetic regulation of muscle gene expression through dynamic interaction with chromatin domains and epigenetic enzymes. We previously showed that lamin A/C interacts with histone deacetylase 2 (HDAC2). In this study, we deepened the relevance and regulation of lamin A/C-HDAC2 interaction in human muscle cells. We present evidence that HDAC2 binding to lamina A/C is related to HDAC2 acetylation on lysine 75 and expression of p300-CBP associated factor (PCAF), an acetyltransferase known to acetylate HDAC2. Our findings show that lamin A and farnesylated prelamin A promote PCAF recruitment to the nuclear lamina and lamin A/C binding in human myoblasts committed to myogenic differentiation, while protein interaction is decreased in differentiating myotubes. Interestingly, PCAF translocation to the nuclear envelope, as well as lamin A/C-PCAF interaction, are reduced by transient expression of lamin A mutated forms causing Emery Dreifuss muscular dystrophy. Consistent with this observation, lamin A/C interaction with both PCAF and HDAC2 is significantly reduced in Emery-Dreifuss muscular dystrophy myoblasts. Overall, these results support the view that, by recruiting PCAF and HDAC2 in a molecular platform, lamin A/C might contribute to regulate their epigenetic activity required in the early phase of muscle differentiation.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y%_48,

title = {Altered adipocyte differentiation and unbalanced autophagy in type 2 Familial Partial Lipodystrophy: an in vitro and in vivo study of adipose tissue browning.},

author = {Pellegrini C and Columbaro M and Schena E and Prencipe S and Andrenacci D and Iozzo P and Angela Guzzardi M and Capanni C and Mattioli E and Loi M and Araujo-Vilar D and Squarzoni S and Cinti S and Morselli P and Giorgetti A and Zanotti L and Gambineri A and Lattanzi G},

url = {https://www.nature.com/articles/s12276-019-0289-0},

doi = {10.1038/s12276-019-0289-0},

year  = {2019},

date = {2019-03-04},

urldate = {2019-03-04},

journal = {Experimental & molecular medicine.},

volume = {51},

number = {8},

pages = {89},

abstract = {Type-2 Familial Partial Lipodystrophy is caused by LMNA mutations. Patients gradually lose subcutaneous fat from the limbs, while they accumulate adipose tissue in the face and neck. Several studies have demonstrated that autophagy is involved in the regulation of adipocyte differentiation and the maintenance of the balance between white and brown adipose tissue. We identified deregulation of autophagy in laminopathic preadipocytes before induction of differentiation. Moreover, in differentiating white adipocyte precursors, we observed impairment of large lipid droplet formation, altered regulation of adipose tissue genes, and expression of the brown adipose tissue marker UCP1. Conversely, in lipodystrophic brown adipocyte precursors induced to differentiate, we noticed activation of autophagy, formation of enlarged lipid droplets typical of white adipocytes, and dysregulation of brown adipose tissue genes. In agreement with these in vitro results indicating conversion of FPLD2 brown preadipocytes toward the white lineage, adipose tissue from FPLD2 patient neck, an area of brown adipogenesis, showed a white phenotype reminiscent of its brown origin. Moreover, in vivo morpho-functional evaluation of fat depots in the neck area of three FPLD2 patients by PET/CT analysis with cold stimulation showed the absence of brown adipose tissue activity. These findings highlight a new pathogenetic mechanism leading to improper fat distribution in lamin A-linked lipodystrophies and show that both impaired white adipocyte turnover and failure of adipose tissue browning contribute to disease.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_74,

title = {Statins and Histone Deacetylase Inhibitors Affect Lamin A/C - Histone Deacetylase 2 Interaction in Human Cells.},

author = {Mattioli E and Andrenacci D and Mai A and Valente S and Robijns J and De Vos WH and Capanni C and Lattanzi G},

url = {https://www.frontiersin.org/articles/10.3389/fcell.2019.00006/full},

doi = {10.3389/fcell.2019.00006},

year  = {2019},

date = {2019-03-08},

urldate = {2019-03-08},

journal = {Frontiers in cell and developmental biology},

volume = {7},

pages = {6},

abstract = {We recently identified lamin A/C as a docking molecule for human histone deacetylase 2 (HDAC2) and showed involvement of HDAC2-lamin A/C complexes in the DNA damage response. We further showed that lamin A/C-HDAC2 interaction is altered in Hutchinson-Gilford Progeria syndrome and other progeroid laminopathies. Here, we show that both inhibitors of lamin A maturation and small molecules inhibiting HDAC activity affect lamin A/C interaction with HDAC2. While statins, which inhibit prelamin A processing, reduce protein interaction, HDAC inhibitors strengthen protein binding. Moreover, treatment with HDAC inhibitors restored the enfeebled lamin A/C-HDAC2 interaction observed in HGPS cells. Based on these results, we propose that prelamin A levels as well as HDAC2 activation status might influence the extent of HDAC2 recruitment to the lamin A/C-containing platform and contribute to modulate HDAC2 activity. Our study links prelamin A processing to HDAC2 regulation and provides new insights into the effect of statins and histone deacetylase inhibitors on lamin A/C functionality in normal and progeroid cells.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_159,

title = {Altered modulation of lamin A/C-HDAC2 interaction and p21 expression during oxidative stress response in HGPS.},

author = {Mattioli E and Andrenacci D and Garofalo C and Prencipe S and Scotlandi K and Remondini D and Gentilini D and {Di Blasio AM} and Valente S and Scarano E and Cicchilitti L and Piaggio G and Mai A and Lattanzi G},

url = {https://onlinelibrary.wiley.com/doi/abs/10.1111/acel.12824},

doi = {10.1111/acel.12824},

year  = {2018},

date = {2018-02-14},

journal = {Aging cell},

volume = {17},

number = {5},

pages = {e1282},

abstract = {Defects in stress response are main determinants of cellular senescence and organism aging. In fibroblasts from patients affected by Hutchinson-Gilford progeria, a severe LMNA-linked syndrome associated with bone resorption, cardiovascular disorders, and premature aging, we found altered modulation of CDKN1A, encoding p21, upon oxidative stress induction, and accumulation of senescence markers during stress recovery. In this context, we unraveled a dynamic interaction of lamin A/C with HDAC2, an histone deacetylase that regulates CDKN1A expression. In control skin fibroblasts, lamin A/C is part of a protein complex including HDAC2 and its histone substrates; protein interaction is reduced at the onset of DNA damage response and recovered after completion of DNA repair. This interplay parallels modulation of p21 expression and global histone acetylation, and it is disrupted by LMNAmutations leading to progeroid phenotypes. In fact, HGPS cells show impaired lamin A/C-HDAC2 interplay and accumulation of p21 upon stress recovery. Collectively, these results link altered physical interaction between lamin A/C and HDAC2 to cellular and organism aging. The lamin A/C-HDAC2 complex may be a novel therapeutic target to slow down progression of progeria symptoms.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_141,

title = {Lamins and bone disorders: current understanding and perspectives.},

author = {Gargiuli C and Schena E and Mattioli E and Columbaro M and D'Apice MR and Novelli G and Greggi T and Lattanzi G},

url = {http://www.oncotarget.com/index.php?journal=oncotarget&page=article&op=view&path[]=25071&pubmed-linkout=1},

doi = {10.18632/oncotarget.25071},

year  = {2018},

date = {2018-04-27},

journal = {Oncotarget},

volume = {9},

number = {32},

pages = {22817-22831},

abstract = {Lamin A/C is a major constituent of the nuclear lamina implicated in a number of genetic diseases, collectively known as laminopathies. The most severe forms of laminopathies feature, among other symptoms, congenital scoliosis, osteoporosis, osteolysis or delayed cranial ossification. Importantly, specific bone districts are typically affected in laminopathies. Spine is severely affected in LMNA-linked congenital muscular dystrophy. Mandible, terminal phalanges and clavicles undergo osteolytic processes in progeroid laminopathies and Restrictive Dermopathy, a lethal developmental laminopathy. This specificity suggests that lamin A/C regulates fine mechanisms of bone turnover, as supported by data showing that lamin A/C mutations activate non-canonical pathways of osteoclastogenesis, as the one dependent on TGF beta 2. Here, we review current knowledge on laminopathies affecting bone and LMNA involvement in bone turnover and highlight lamin-dependent mechanisms causing bone disorders. This knowledge can be exploited to identify new therapeutic approaches not only for laminopathies, but also for other rare diseases featuring bone abnormalities.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1.%Y_146,

title = {Network assessment of demethylation treatment in melanoma: Differential transcriptome-methylome and antigen profile signatures.},

author = {Jiang Z and Cinti C and Taranta M and Mattioli E and Schena E and Singh S and Khurana R and Lattanzi G and Tsinoremas NF and Capobianco E},

url = {https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0206686},

doi = {10.1371/journal.pone.0206686},

year  = {2018},

date = {2018-02-21},

journal = { PLoS One},

volume = {13},

issue = {11},

pages = {e0206686},

abstract = {Background: In melanoma, like in other cancers, both genetic alterations and epigenetic underlie the metastatic process. These effects are usually measured by changes in both methylome and transcriptome profiles, whose cross-correlation remains uncertain. We aimed to assess at systems scale the significance of epigenetic treatment in melanoma cells with different metastatic potential. Methods and findings: Treatment by DAC demethylation with 5-Aza-2'-deoxycytidine of two melanoma cell lines endowed with different metastatic potential, SKMEL-2 and HS294T, was performed and high-throughput coupled RNA-Seq and RRBS-Seq experiments delivered differential profiles (DiP) of both transcriptomes and methylomes. Methylation levels measured at both TSS and gene body were studied to inspect correlated patterns with wide-spectrum transcript abundance levels quantified in both protein coding and non-coding RNA (ncRNA) regions. The DiP were then mapped onto standard bio-annotation sources (pathways, biological processes) and network configurations were obtained. The prioritized associations for target identification purposes were expected to elucidate the reprogramming dynamics induced by the epigenetic therapy. The interactomic connectivity maps of each cell line were formed to support the analysis of epigenetically re-activated genes. i.e. those supposedly silenced by melanoma. In particular, modular protein interaction networks (PIN) were used, evidencing a limited number of shared annotations, with an example being MAPK13 (cascade of cellular responses evoked by extracellular stimuli). This gene is also a target associated to the PANDAR ncRNA, therapeutically relevant because of its aberrant expression observed in various cancers. Overall, the non-metastatic SKMEL-2 map reveals post-treatment re-activation of a richer pathway landscape, involving cadherins and integrins as signatures of cell adhesion and proliferation. Relatively more lncRNAs were also annotated, indicating more complex regulation patterns in view of target identification. Finally, the antigen maps matched to DiP display other differential signatures with respect to the metastatic potential of the cell lines. In particular, as demethylated melanomas show connected targets that grow with the increased metastatic potential, also the potential target actionability seems to depend to some degree on the metastatic state. However, caution is required when assessing the direct influence of re-activated genes over the identified targets. In light of the stronger treatment effects observed in non-metastatic conditions, some limitations likely refer to in silico data integration tools and resources available for the analysis of tumor antigens. Conclusion: Demethylation treatment strongly affects early melanoma progression by re-activating many genes. This evidence suggests that the efficacy of this type of therapeutic intervention is potentially high at the pre-metastatic stages. The biomarkers that can be assessed through antigens seem informative depending on the metastatic conditions, and networks help to elucidate the assessment of possible targets actionability.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_160,

title = {Samp1 Mislocalization in Emery-Dreifuss Muscular Dystrophy.},

author = {Mattioli E and Columbaro M and Jafferali MH and Schena E and Hallberg E and Lattanzi G},

url = {https://www.mdpi.com/2073-4409/7/10/170},

doi = {10.3390/cells7100170},

year  = {2018},

date = {2018-10-19},

urldate = {2015-10-15},

journal = {Cells},

volume = {7},

number = {10},

pages = {pii: E170},

abstract = {pii: E170},

keywords = {},

pubstate = {published},

tppubtype = {article}

}