Preferential occupancy of histone variant H2AZ at inactive promoters influences local histone modifications and chromatin remodeling

Abstract

The yeast histone variant H2AZ (Htz1) is implicated in transcription activation, prevention of the ectopic spread of heterochromatin, and genome integrity. Our genome-wide localization analysis revealed that Htz1 is widely, but nonrandomly, distributed throughout the genome in an SWR1-dependent manner. We found that Htz1 is enriched in intergenic regions compared with coding regions. Its occupancy is inversely proportional to transcription rates and the enrichment of the RNA polymerase II under different growth conditions. However, Htz1 does not seem to directly regulate transcription repression genome-wide; instead, the presence of Htz1 under the inactivated condition is essential for optimal activation of a subset of genes. In addition, Htz1 is not generally responsible for nucleosome positioning, even at those promoters where Htz1 is highly enriched. Finally, using a biochemical approach, we demonstrate that incorporation of Htz1 into nucleosomes inhibits activities of histone modifiers associated with transcription, Dot1, Set2, and NuA4 and reduces the nucleosome mobilization driven by chromatin remodeling complexes. These lines of evidence collectively suggest that Htz1 may serve to mark quiescent promoters for proper activation.htz1 ͉ transcription ͉ nucleosome

Mechanisms of ATP dependent chromatin remodeling

“…Htz1 has a role in transcription and can also act as a barrier inhibiting spread of silent telomeric and mating locus heterochromatin into transcriptionally active regions. SWR1 dependent deposition of Htz1 was observed at telomeres (which requires Yaf9 component) [119], centromeres [120] and other intergenic regions [121]. Biochemical analyses have shown that Swc2 component binds Htz1 physically and is needed for Htz1 deposition [122].…”

The γ‐H2A.X: Is it just a surrogate marker of double‐strand breaks or much more?

“…H2ABbd is the smallest H2A variant, has a distinct N terminus, and is excluded from the Xi chromosome in mammalian cells [Chadwick and Willard, 2001]. H2A.Z and H2A.X are minor H2A variants that appear constitutively expressed and localize throughout the genome, although H2A.Z shows some enrichment in intergenic regions [Li et al, 2005]. Interestingly, the major H2A proteins in Saccharomyces cerevisiae and Schizosaccharomyces pombe are more similar to the mammalian H2A.X variant than the major mammalian H2A subtypes [Malik and Henikoff, 2003].…”

Nucleosome fragility is associated with future transcriptional response to developmental cues and stress inC. elegans

“…Results from yeast (Weiner et al 2010;Xi et al 2011;Kubik et al 2015), plants (Vera et al 2014), mouse (Lombraña et al 2013;Deng et al 2015;Iwafuchi-Doi et al 2016;Mieczkowski et al 2016), worm (Ooi et al 2010), and fly (Henikoff et al 2009; have identified highly labile nucleosomes in 5 ′ and 3 ′ "nucleosome-free" regions. In yeast, Xi et al (2011) observed that fragile nucleosomes were associated with H2A.Z-containing promoter nucleosomes, believed to be involved in stress response (Li et al 2005;Zhang et al 2005). In vertebrates, individual nucleosomes containing both H3.3 and H2A.Z histone variants are unstable (Jin and Felsenfeld 2007;Jin et al 2009).…”