Dynamics of Polycomb and Trithorax activities during development

Abstract

Dynamic changes in gene expression are tightly controlled during development, as a single totipotent zygote gives rise to distinct cell lineages. The establishment and maintenance of these diverse transcriptional programs rely on changes of chromatin state, mainly through histone modifications. Polycomb and Trithorax complexes participate in setting apart active and inactive genes by respectively repressing and activating key developmental regulators in different cell types. Over the last decade, our understanding of the biochemical mechanisms underlying their activities has greatly improved, but the signals targeting these proteins to specific regions of the genome are still poorly understood, particularly in vertebrates. Recent findings highlight the highly dynamic activities of Polycomb and Trithorax complexes in vivo. Surprisingly, although their role in transcriptional regulation is deeply conserved during evolution, the time sequence in which they act seems to vary across species.

Controlling Hox gene expression and activity to build the vertebrate axial skeleton

“…In particular, M33 mutant embryos have facilitated access to RA responsive elements within the Hoxd cluster, because low RA doses produce premature Hox gene activation and homeotic transformations in the axial skeleton of these mutants. This is consistent with a more labile repressed state of the Hox clusters in the absence of M33 and suggests that, in addition to their well‐known function in epigenetic maintenance of positional identity (reviewed in Soshnikova, ), PcG proteins may also play an essential role in the early repression of Hox genes. Clear evidence for this is still lacking and awaits further investigation.…”

Chromatin organization and global regulation ofHoxgene clusters

“…Similar to their Drosophila orthologues, PcG and trxG genes are required for vertebrate embryonic development, and mutations in these genes lead to a deregulation of Hox genes, amongst other defects (reviewed in [46,47]). Recently, a progressive loss of H3K27me3, concomitantly to a gain of H3K4me3, was observed together with the sequential activation of Hoxd genes during the extension of the main body axis in the mouse in vivo ([48]; figure 1 a ).…”

Epigenetic Regulation of Pluripotency by Polycomb Group Proteins

“…Interestingly, a subset of PcG targets was also found occupied by classical stemness factors that are required for the propagation of undifferentiated embryonic stem cells (ESCs), suggesting that PcG recruitment is needed to repress lineagespecific targets in these cells ; Lee et al 2006). Thus, PcG repression was found to be a widespread mechanism that stably keeps the inactive state of mainly differentiation-specific targets, but this repression is dynamic and can, if developmental processes render it necessary, be reversed (Soshnikova 2011). In the following review it will be outlined that PcG proteins have a crucial role in silencing developmental regulators in pluripotent cells and thus for the maintenance of stemness.…”