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

Chandra, T. et al. (2012) Independence of repressive histone marks and chromatin compaction during senescent heterochromatic layer formation. Molecular Cell, 47(2), pp. 203-214. (doi: 10.1016/j.molcel.2012.06.010) (PMID:22795131) (PMCID:PMC3701408)

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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.

Item Type:Articles
Glasgow Author(s) Enlighten ID:Kirschner, Dr Kristina
Authors: Chandra, T., Kirschner, K., Thuret, J.-Y., Pope, B. D., Ryba, T., Newman, S., Ahmed, K., Samarajiwa, S. A., Salama, R., Carroll, T., Stark, R., Janky, R.'s., Narita, M., Xue, L., Chicas, A., Nũnez, S., Janknecht, R., Hayashi-Takanaka, Y., Wilson, M. D., Marshall, A., Odom, D. T., Babu, M. M., Bazett-Jones, D. P., Tavaré, S., Edwards, P. A.W., Lowe, S. W., Kimura, H., Gilbert, D. M., and Narita, M.
College/School:College of Medical Veterinary and Life Sciences > School of Cancer Sciences
Journal Name:Molecular Cell
ISSN (Online):1097-4164
Published Online:12 July 2012

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