Causal role for inheritance of H3K27me3 in maintaining the OFF state of a Drosophila HOX gene

Abstract

Many eukaryotic cells can respond to transient environmental or developmental stimuli with heritable changes in gene expression that are associated with nucleosome modifications. However, it remains uncertain whether modified nucleosomes play a causal role in transmitting such epigenetic memories, as opposed to controlling or merely reflecting transcriptional states inherited by other means. Here, we provide in vivo evidence that H3K27 trimethylated nucleosomes, once established at a repressed Drosophila HOX gene, remain heritably associated with that gene and can carry the memory of the silenced state through multiple rounds of replication, even when the capacity to copy the H3K27me3 mark to newly incorporated nucleosomes is diminished or abolished. Hence, in this context, the inheritance of H3K27 trimethylation conveys epigenetic memory.

The impact of cellular metabolism on chromatin dynamics and epigenetics

“…promoters, enhancers and exons) 7–10, 12–14 . Thus, there is tremendous potential for these posttranslational modifications to have profound effects on gene expression and substantial ongoing efforts aim to understand the structure and function of chromatin modifications 10, 11, 15–19 . Chromatin and nucleic acid modifications, when inherited after cell division, or in offspring after reproduction (e.g.…”

The essential and multifunctional TFIIH complex

“…Although the term “epigenetic” has taken on various meanings, a strict definition requires a heritable trait that does not result from a change in genomic DNA sequence. DNA CpG methylation is considered heritable, and emerging evidence suggests histone marks can also be heritable . The transcription‐associated histone marks that are affected by CDK7 kinase activity, H3K4me3 and H3K36me3, are each linked to DNA methylation.…”

RNA-mediated regulation of heterochromatin

“…PRC2 is a large multi-subunit protein complex with many essential and accessory factors [28]. PRC2 associates with Polycomb Responsive Elements (PREs) in the fly genome, which are necessary for maintenance of silencing over multiple rounds of DNA replication; however, in non-dividing cells, PRC2 localizes independent of these DNA sequences [29,30], and may depend on other interactors such as H3K27 methylation and RNA. Mammalian PRC2 binds RNA through the H3K27 methyltransferase subunit EZH2 and the subunit Eed; but other subunits and modifications can affect RNA binding affinity and specificity [8,31].…”