A Key Role for Chd1 in Histone H3 Dynamics at the 3′ Ends of Long Genes in Yeast

Abstract

Chd proteins are ATP–dependent chromatin remodeling enzymes implicated in biological functions from transcriptional elongation to control of pluripotency. Previous studies of the Chd1 subclass of these proteins have implicated them in diverse roles in gene expression including functions during initiation, elongation, and termination. Furthermore, some evidence has suggested a role for Chd1 in replication-independent histone exchange or assembly. Here, we examine roles of Chd1 in replication-independent dynamics of histone H3 in both Drosophila and yeast. We find evidence of a role for Chd1 in H3 dynamics in both organisms. Using genome-wide ChIP-on-chip analysis, we find that Chd1 influences histone turnover at the 5′ and 3′ ends of genes, accelerating H3 replacement at the 5′ ends of genes while protecting the 3′ ends of genes from excessive H3 turnover. Although consistent with a direct role for Chd1 in exchange, these results may indicate that Chd1 stabilizes nucleosomes perturbed by transcription. Curiously, we observe a strong effect of gene length on Chd1's effects on H3 turnover. Finally, we show that Chd1 also affects histone modification patterns over genes, likely as a consequence of its effects on histone replacement. Taken together, our results emphasize a role for Chd1 in histone replacement in both budding yeast and Drosophila melanogaster, and surprisingly they show that the major effects of Chd1 on turnover occur at the 3′ ends of genes.

A nucleosome turnover map reveals that the stability of histone H4 Lys20 methylation depends on histone recycling in transcribed chromatin

“…ATPdependent chromatin remodelers regulate nucleosome dynamics at the promoter regions surrounding the TSS, but to our knowledge, no chromatin remodeler has been reported at the TES. As mentioned earlier, in mouse, Drosophila, and S. cerevisiae, the remodeling protein Chd1 primarily acts around the TSS but also appears to stimulate histone recycling in the gene body during Pol II elongation (Radman-Livaja et al 2012;Skene et al 2014).…”

“…Nucleosome turnover in promoter regions is directly affected by ATP-dependent chromatin remodelers such as Ino80, which binds to the 5 ′ NDR and promotes turnover of TSS nucleosomes (Yen et al 2013). In mouse, Drosophila, and Saccharomyces cerevisiae, Chd1 has been found to promote the turnover of nucleosomes surrounding the 5 ′ NDR but suppresses turnover at the end of the gene (Radman-Livaja et al 2012;Skene et al 2014). In general, nucleosome turnover appears to correlate with gene transcription Huang et al 2013;Kraushaar et al 2013).…”

Histone exchange, chromatin structure and the regulation of transcription

“…4d). The yeast remodeller Chd1 shows a similar chromatin-resetting function 121,125 , although it does not seem to be recruited by H3K36 methylation (FIG. 4d).…”

A Role for Monomethylation of Histone H3-K27 in Gene Activity inDrosophila

“…In particular, Set2, the H3-K36-methylating enzyme, can be recruited to elongating RNA polII via binding to its C-terminal domain (CTD) repeats bearing phosphorylated serine-2 and serine-5 (LI et al 2003;LI et al 2005). Once in place, K36 methylation is implicated in resetting chromatin altered by RNA polII passage; thus, K36me3 suppresses further histone exchange , activates HDAC(s) to restore a hypoacetylated histone state (CARROZZA et al 2005;JOSHI and STRUHL 2005), and promotes re-establishment of regularly-spaced nucleosomes by recruiting the ISWI chromatin remodeler as well as CHD1 (RADMAN-LIVAJA et al 2012;SMOLLE et al 2012). Intriguingly, another co-transcriptional remodeler, Kismet (CHD7), promotes K36 methylation in Drosophila (DORIGHI and TAMKUN 2013).…”