SAMMY-seq reveals early alteration of heterochromatin and deregulation of bivalent genes in Hutchinson-Gilford Progeria Syndrome
| Autor: | Cristiano Petrini, Chiara Lanzuolo, Gennaro Oliva, Endre Sebestyén, Federica Lucini, Sara Valsoni, Francesco Ferrari, Louis Antonelli, Andrea Bianchi, Francesco Gregoretti, Fabrizia Marullo, Ilaria Olivieri |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
General Physics and Astronomy Datasets as Topic Polycomb-Group Proteins Hutchinson-Gilford Progeria Syndrome Histones 0302 clinical medicine Progeria Heterochromatin Histone post-translational modifications RNA-Seq Child Cells Cultured Skin Multidisciplinary integumentary system SAMMY-seq Lamin Type A Chromatin Cell biology Histone Code Child Preschool embryonic structures Chromatin Immunoprecipitation Sequencing Transcriptional Activation congenital hereditary and neonatal diseases and abnormalities Science Primary Cell Culture Biology General Biochemistry Genetics and Molecular Biology Chromatin remodeling Bivalent (genetics) Article 03 medical and health sciences Chromatin analysis medicine Humans Psychological repression Gene Nuclear organization fungi nutritional and metabolic diseases General Chemistry Fibroblasts medicine.disease Gene regulation 030104 developmental biology 030217 neurology & neurosurgery Lamin |
| Zdroj: | Nature Communications Nature Communications, Vol 11, Iss 1, Pp 1-16 (2020) Nature communications 11 (2020): 6274. doi:10.1038/s41467-020-20048-9 info:cnr-pdr/source/autori:Sebestyen E, Marullo F, Lucini F, Petrini C, Bianchi A, Valsoni S, Olivieri I, Antonelli L, Gregoretti F, Oliva G, Ferrari F, Lanzuolo C./titolo:SAMMY-seq reveals early alteration of heterochromatin and deregulation of bivalent genes in Hutchinson-Gilford Progeria Syndrome/doi:10.1038%2Fs41467-020-20048-9/rivista:Nature communications/anno:2020/pagina_da:6274/pagina_a:/intervallo_pagine:6274/volume:11 |
| ISSN: | 2041-1723 |
| Popis: | Hutchinson-Gilford progeria syndrome is a genetic disease caused by an aberrant form of Lamin A resulting in chromatin structure disruption, in particular by interfering with lamina associated domains. Early molecular alterations involved in chromatin remodeling have not been identified thus far. Here, we present SAMMY-seq, a high-throughput sequencing-based method for genome-wide characterization of heterochromatin dynamics. Using SAMMY-seq, we detect early stage alterations of heterochromatin structure in progeria primary fibroblasts. These structural changes do not disrupt the distribution of H3K9me3 in early passage cells, thus suggesting that chromatin rearrangements precede H3K9me3 alterations described at later passages. On the other hand, we observe an interplay between changes in chromatin accessibility and Polycomb regulation, with site-specific H3K27me3 variations and transcriptional dysregulation of bivalent genes. We conclude that the correct assembly of lamina associated domains is functionally connected to the Polycomb repression and rapidly lost in early molecular events of progeria pathogenesis. Hutchinson-Gilford progeria syndrome is a genetic disease where an aberrant form of Lamin A disrupts chromatin by interfering with lamina associated domains. Here, the authors present the SAMMY-seq, a method for genome-wide characterization of heterochromatin dynamics and detect early stage alterations of heterochromatin structure in progeria primary fibroblasts, accompained by Polycomb dysfunctions. |
| Databáze: | OpenAIRE |
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