In this election season, few people are on the fence about their choice for U.S. president. But histone H2A.Z seemingly votes on both sides of the transcription —hanging out at active regulatory elements and at repressive ones. Researchers in Boston figured out how H2A.Z does this, and it may have to do with the different mods on it.
They looked at H2A.Z in mouse and human embryonic stem (ES) cells and in mouse neural progenitor cells. Here’s what they found:
- In both ES cell types, H2A.Z was enriched at H3K4me3-only (active) and bivalent, Polycomb-target (silenced, but poised) promoters, but was absent from stably repressed promoters.
- In mouse neural progenitor cells, which are more differentiated, H2A.Z is again at active promoters. But in these cells, H2A.Z is at a subset of Polycomb targets—only those that also have H3K4me3. Thus, as differentiation happens, it seems that H2A.Z leaves those Polycomb-targeted promoters that lose the H3K4me3 mark and end up with only H3K27me3 (repressive).
- H2A.Z is associated with all types of methylated H3K4—mon-, di-, and trimethylated forms, which are found at active promoters and enhancers. Also, H2A.Z sites are near regions lacking nucleosomes that are actively transcribed.
- They found both monoubiquitinated and dually modified H2A.Z (acetylated and ubiquitinated) at bivalent promoters.
- Acetylated H2A.Z was at poised and active promoters.
The team says, “Our findings associate H2A.Z with functionally distinct genomic elements, and suggest that posttranslational modifications may reconcile its contrasting locations and roles.”
Read the paper at Genome Biology October 2012.