Histone replacement marks the boundaries of cis-regulatory domains

One of the still unsolved questions is how the epigenetic memory is maintained in regulatory regions, and passed through generations. Previously, Mito et al. (2005), developed an strategy to identify patterns of histone replacement at a genomic scale. In this report, they used that biotin epitope tag approach to measure the histone H3.3 (that is found throughout the cell cycle) to H3 (deposited during replication) ratio in premitotic Drosophila homeotic genes. They found that the replacement of histones and nucleosome occupancy is distinctive in cis- regulatory regions; and they suggest a cyclic model for this process:

What process maintains the chromatin of cis-regulatory elements in a state of flux? Many DNA- binding and chromatin- binding proteins involved in gene regulation display short residence times on DNA, and some mouse transcription factors show dynamic behavior at their functional binding sites. A model for this process has been proposed, involving alternating cycles of nucleosome disruption by a Brahma- related SWI/SNF chromatin-remodeler and transcription factor binding. The binding of PcG and trxG proteins is also dynamic, and we propose that a similar cycle of nucleosome disruption and factor binding takes place at boundaries and PREs. Nucleosome disruption by SWI/SNF remodeling complexes would occasionally evict nucleosomes and transiently expose DNA, which would become available to other diffusible factors, including PcG proteins. The continued local presence of nucleosome remodelers would result in another cycle of remodeling, nucleosome depletion, nuclease hypersensitivity, and histone replacement at the site. […] The resulting dynamic process would allow for proteins that promote opposite epigenetic outcomes to act at common cis-regulatory sites.

Mito Y. et al. 2007. Science, Vol. 315(5817):1408-1411

epigenetics

More comments can be found in this issue of Science STKE, and at the Faculty of 1000 website. Also, a related paper from the same issue of Science by Dion et al., was previously discussed here.