@article{3f492dd6547e4a6baeca138c32b5ad9e,
title = "Independence of Repressive Histone Marks and Chromatin Compaction during Senescent Heterochromatic Layer Formation",
abstract = "The expansion of repressive epigenetic marks has been implicated in heterochromatin formation during embryonic development, but the general applicability of this mechanism is unclear. Here we show that nuclear rearrangement of repressive histone marks H3K9me3 and H3K27me3 into nonoverlapping structural layers characterizes senescence-associated heterochromatic foci (SAHF) formation in human fibroblasts. However, the global landscape of these repressive marks remains unchanged upon SAHF formation, suggesting that in somatic cells, heterochromatin can be formed through the spatial repositioning of pre-existing repressively marked histones. This model is reinforced by the correlation of presenescent replication timing with both the subsequent layered structure of SAHFs and the global landscape of the repressive marks, allowing us to integrate microscopic and genomic information. Furthermore, modulation of SAHF structure does not affect the occupancy of these repressive marks, nor vice versa. These experiments reveal that high-order heterochromatin formation and epigenetic remodeling of the genome can be discrete events.",
author = "Tamir Chandra and Kristina Kirschner and Thuret, {Jean Yves} and Pope, {Benjamin D.} and Tyrone Ryba and Scott Newman and Kashif Ahmed and Samarajiwa, {Shamith A.} and Rafik Salama and Thomas Carroll and Rory Stark and Janky, {Rekin's S.} and Masako Narita and Lixiang Xue and Agustin Chicas and Sabrina Nũnez and Ralf Janknecht and Yoko Hayashi-Takanaka and Wilson, {Michael D.} and Aileen Marshall and Odom, {Duncan T.} and Babu, {M. Madan} and Bazett-Jones, {David P.} and Simon Tavar{\'e} and Edwards, {Paul A.W.} and Lowe, {Scott W.} and Hiroshi Kimura and Gilbert, {David M.} and Masashi Narita",
note = "Funding Information: We thank R. Didier for assistance with flow cytometry; A. Straight (CENPA Ab), D. Reinberg (H3K27me2/3 Ab), M. Ferguson-Smith (sorted chromosomes), and I. Roberts (a-satellite vector) for reagents; A. Young, M. Hoare, J. Nakayama, and K. Hamada for critical reading of the manuscript; L. Blackburn for editing; and the CRI core facilities (Genomics, Bioinformatics, and Microscopy) for technical support. We thank the Cambridge NIHR Biomedical Research Centre, who fund and support the Addenbrooke's Hospital Tissue Bank. This work was supported by the University of Cambridge, Cancer Research UK, Hutchison Whampoa, the UK Medical Research Council, the Human Frontier Science Program (M.N. and R.S.), JST CREST and grants-in-aid from the MEXT of Japan (H.K. and Y.H.-T.), the Canadian Institutes of Health Research (D.P.B.-J.), and National Institute of General Medicine grants GM083337 and GM085354 (D.M.G.). D.P.B.-J. holds the Canada Research Chair in Molecular and Cellular Imaging. ",
year = "2012",
month = jul,
day = "27",
doi = "10.1016/j.molcel.2012.06.010",
language = "English",
volume = "47",
pages = "203--214",
journal = "Molecular cell",
issn = "1097-2765",
number = "2",
}