Independence of repressive histone marks and chromatin compaction during senescent heterochromatic layer formation

Tamir Chandra, Kristina Kirschner, Jean-Yves Thuret, Benjamin D Pope, Tyrone Ryba, Scott Newman, Kashif Ahmed, Shamith A Samarajiwa, Rafik Salama, Thomas Carroll, Rory Stark, Rekin's Janky, Masako Narita, Lixiang Xue, Agustin Chicas, Sabrina Nũnez, Ralf Janknecht, Yoko Hayashi-Takanaka, Michael D Wilson, Aileen MarshallDuncan T Odom, M Madan Babu, David P Bazett-Jones, Simon Tavaré, Paul A W Edwards, Scott W Lowe, Hiroshi Kimura, David M Gilbert, Masashi Narita

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)203-14
Number of pages12
JournalMolecular Cell
Volume47
Issue number2
DOIs
Publication statusPublished - 27 Jul 2012

Keywords

  • Bromodeoxyuridine
  • Cell Aging
  • Chromatin
  • Chromosomes
  • Epigenesis, Genetic
  • Fibroblasts
  • Gene Expression Regulation, Developmental
  • Gene Silencing
  • Genome
  • Genome-Wide Association Study
  • Heterochromatin
  • Histones
  • Humans
  • Laser Scanning Cytometry
  • Microscopy, Fluorescence

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