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. 2013 Jan-Feb;4(1):23-8.
doi: 10.4161/nucl.23189. Epub 2012 Dec 11.

High-order chromatin structure and the epigenome in SAHFs

Tamir Chandra  1 , Masashi Narita
Affiliations

High-order chromatin structure and the epigenome in SAHFs

Tamir Chandra et al. Nucleus. 2013 Jan-Feb.

Abstract

It is almost ten years since senescence associated heterochromatic foci (SAHFs) were first described in human diploid fibroblasts (HDFs). Since then, a number of factors have been identified that affect SAHF formation, including HMGA proteins, structural components of SAHFs. However, the involvement of epigenetic marks in SAHF formation remains unclear. Our recent study, combining microscopy and ChIP-seq approaches, revealed that SAHFs are formed through spatial repositioning of the genome. This occurs according to certain chromatin features that are correlated with, but do not require, the repressive marks histone H3 trimethylated on lysine 9 (H3K9me3) and H3K27me3. These repressive marks are segregated from each other within SAHFs, forming layered high-order chromatin structures (HOCS). During the dynamic change in HOCS as SAHFs form, the linear epigenomic profiles of these repressive marks are highly static. This is in marked contrast to the spreading of repressive marks occurring during embryonic cell differentiation. Thus the layered HOCS of SAHFs is likely achieved mainly through the spatial rearrangement of pre-existing heterochromatin, rather than spreading of heterochromatin. Evidence for the co-association of similar types of chromatin is emerging and SAHFs may provide a unique model system to study the correlation between HOCS and chromatin types, which are readily visible and regulable.

Keywords: SAHF; epigenomics; heterochromatin; histone marks; senescence.

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Figures

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Figure 1. SAHF chromatin is rearranged into a H3K9me3 core and a H3K27me3 ring. (A) Confocal images of indirect immunofluorescence for H3K9me3 (green) and H3K27me3 (red) for growing or Ras-induced senescent IMR90 fibroblasts. The inset shows one SAHF magnified. Xi represents the inactive X chromosome. (B) A model for chromatin arrangement in growing and SAHF cells is shown.
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Figure 2. Chromatin pattern dynamics at different resolutions. (A) Chromosome-wide landscape of H3K27me3 in Growing and Ras-induced senescent IMR90 fibroblasts (reanalysed from ref. 8). ChIP-seq data intensities have been windowed in 1kb bins. A rolling mean of 1000 units has been applied. The plot shows a globally static landscape of H3K27me3 between Growing and Senescent cells. The black rectangle approximately indicates the position of CDKN2A (also called p16INK4A) on chromosome 9. (B) A uniformly scaled UCSC genome browser shot of H3K27me3 ChIP-seq in Growing and Ras-induced senescent cells for the CDKN2A locus. Note, CDKN2A is a marker of senescence and its transcription is activated during Ras-induced senescence.
See this image and copyright information in PMC

Comment on

  • Chandra T, Kirschner K, Thuret JY, Pope BD, Ryba T, Newman S, Ahmed K, Samarajiwa SA, Salama R, Carroll T, Stark R, Janky R, Narita M, Xue L, Chicas A, Nũnez S, Janknecht R, Hayashi-Takanaka Y, Wilson MD, Marshall A, Odom DT, Babu MM, Bazett-Jones DP, Tavaré S, Edwards PA, Lowe SW, Kimura H, Gilbert DM, Narita M. Independence of repressive histone marks and chromatin compaction during senescent heterochromatic layer formation. Mol Cell. 2012;47:203–14. doi: 10.1016/j.molcel.2012.06.010. doi: 10.1016/j.molcel.2012.06.010

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