The Euchromatic and Heterochromatic Landscapes Are Shaped by Antagonizing Effects of Transcription on H2A.Z Deposition

Abstract

A role for variant histone H2A.Z in gene expression is now well established but little is known about the mechanisms by which it operates. Using a combination of ChIP–chip, knockdown and expression profiling experiments, we show that upon gene induction, human H2A.Z associates with gene promoters and helps in recruiting the transcriptional machinery. Surprisingly, we also found that H2A.Z is randomly incorporated in the genome at low levels and that active transcription antagonizes this incorporation in transcribed regions. After cessation of transcription, random H2A.Z quickly reappears on genes, demonstrating that this incorporation utilizes an active mechanism. Within facultative heterochromatin, we observe a hyper accumulation of the variant histone, which might be due to the lack of transcription in these regions. These results show how chromatin structure and transcription can antagonize each other, therefore shaping chromatin and controlling gene expression.

Random deposition of histone variants: A cellular mistake or a novel regulatory mechanism?

“…23 The first conclusion from that observation was that what we had considered as "background" did not simply represent technical background hybridization signal on the array. It rather suggested that some level of H2A.Z incorporates in the genome outside the well characterized "peaks" found at promoters and other regulatory elements.…”

“…[23][24][25] Having so many different locations for a histone variant is very intriguing. Here, we review recent work suggesting that multiple routes can be used to incorporate H2A.Z in the genome and propose that this may lead to different functions for the histone variant.…”

Reconciling the positive and negative roles of histone H2A.Z in gene transcription

“…[56][57][58][59][60][61] Until recently, histone in transcription. 41 Intriguingly, in heterochromatic, pericentromeric or subtelomeric regions, H2A.Z is found on vast chromosomal regions of several hundred kilobases wide. In these regions, H2A.Z is non-acetylated and colocalizes with marks associated with facultative heterochromatin, such as dimethylation of lysine 9 of histone H3 (H3K9me2).…”

“…In these regions, H2A.Z is non-acetylated and colocalizes with marks associated with facultative heterochromatin, such as dimethylation of lysine 9 of histone H3 (H3K9me2). 41 The deposition of H2A.Z within chromatin is thought to be generally catalyzed by ATP-dependent protein complexes. In budding yeast, the Swr1 complex (Swr1.com), named after its catalytic subunit Swr1, interacts with H2A.Z and is necessary for H2A.Z deposition.…”

Changes in H2A.Z occupancy and DNA methylation during B-cell lymphomagenesis

“…For example, H2A.Z is enriched at active gene promoters, as well as at enhancer and insulator elements in terminally differentiated cells from chicken, mouse, and human, suggesting a positive role in regulating gene expression (Bruce et al 2005;Thambirajah et al 2006;Barski et al 2007). Indeed, activation of a gene often includes promoter chromatin remodeling and incorporation of H2A.Z into nucleosomes surrounding the transcriptional start site (TSS) (Gevry et al 2009;Hardy et al 2009). H2A.Z is also localized to Polycomb protein binding sites in murine embryonic stem (ES) cells, suggesting a role in potentiating gene expression (Creyghton et al 2008).…”