Chromatin dynamics and in vitro biomarkers in laminopathies: an overview
© Lattanzi 2015
Published: 11 November 2015
Chromatin regulation in eukaryotes occurs through complex and interconnected mechanisms that ensure heterochromatin maintenance and compartmentalization of chromosome domains, genome stability, chromatin conformational changes before and after mitosis, gene silencing and transcriptional activation and chromatin remodeling at specific promoters. We refer to these events as a whole using the term “chromatin dynamics.” Chromatin dynamics involves a number of protein families including epigenetic enzymes, DNA repair factors, heterochromatin proteins, transcription factors and transcriptional regulators. Although lamins have been involved in almost all the processes that regulate chromatin dynamics, three main functions link lamins to chromatin regulation: recruitment of the DNA damage response proteins, transcription factor binding[3, 4] and modulation and maintenance of heterochromatin domains. Our preliminary data have shown that lamin A/C plays a major role in anchorage of epigenetic enzymes in nuclei and loss of lamin A/C- histone deacetylase (HDAC) binding, as occurs in Hutchinson-Gilford progeria (HGPS) cells, affects enzyme activity and histone acetylation. These results may explain our previously published data showing that the heterochromatin defects of HGPS cells can be rescued by combined inhibition of prelamin A farnesylation and HDAC activity and pave the way to new therapeutic perspectives. Moreover, altered lamin A/C-HDAC interaction and histone acetylation patterns can be explored as potential biomarkers for laminopathies.
- Camozzi D, Capanni C, Cenni V, Mattioli E, Columbaro M, Squarzoni S, et al: Diverse lamin-dependent mechanisms interact to control chromatin dynamics. Focus on laminopathies. Nucleus. 2014, 5 (5): 427-40.PubMedPubMed CentralView ArticleGoogle Scholar
- Lattanzi G, Ortolani M, Columbaro M, Prencipe S, Mattioli E, Lanzarini C, et al: Lamins are rapamycin targets that impact human longevity: a study in centenarians. Journal of cell science. 2014, 127 (Pt 1): 147-57.PubMedView ArticleGoogle Scholar
- Capanni C, Mattioli E, Columbaro M, Lucarelli E, Parnaik VK, Novelli G, et al: Altered pre-lamin A processing is a common mechanism leading to lipodystrophy. Human molecular genetics. 2005, 14 (11): 1489-502.PubMedView ArticleGoogle Scholar
- Columbaro M, Mattioli E, Maraldi NM, Ortolani M, Gasparini L, D'Apice MR, et al: Oct-1 recruitment to the nuclear envelope in adult-onset autosomal dominant leukodystrophy. Biochimica et biophysica acta. 2013, 1832 (3): 411-20.PubMedView ArticleGoogle Scholar
- Lattanzi G, Columbaro M, Mattioli E, Cenni V, Camozzi D, Wehnert M, et al: Pre-Lamin A processing is linked to heterochromatin organization. Journal of cellular biochemistry. 2007, 102 (5): 1149-59.PubMedView ArticleGoogle Scholar
- Columbaro M, Capanni C, Mattioli E, Novelli G, Parnaik VK, Squarzoni S, et al: Rescue of heterochromatin organization in Hutchinson-Gilford progeria by drug treatment. Cellular and molecular life sciences: CMLS. 2005, 62 (22): 2669-78.PubMedPubMed CentralView ArticleGoogle Scholar
This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.