Two possible modes of pioneering associated with combinations of H2A.Z and p300/CBP at nucleosome-occupied enhancers

Cauchy, Pierre; Koch, Frank‐Thomas; Andrau, Jean-Christophe

doi:10.1080/21541264.2017.1291395

Cited by 9 publications

(3 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Recently, we have extended these observations also to developmental signaling pathways: H2A.Z localizes at Notch responsive enhancers where it plays a negative role with regards to the expression of Notch target genes [57]. Interestingly, it has been observed that pioneering factors-bound enhancers exist with two different H2A.Z distributions: a) H2A.Z localizes at the center of Ets1- and Oct4-bound enhancer sites, whereas b) it is enriched at nucleosomes flanking forkhead box protein A2 (FoxA2) or C/EBPα-bound enhancer sites [167]. Table 4 provides the complete list of enhancers, which are bound by signal-specific TFs and have been linked to H2A.Z-mediated regulation.…”

Section: H2az At Enhancers and Promotersmentioning

confidence: 99%

The histone variant H2A.Z in gene regulation

Giaimo

Ferrante

Herchenröther

et al. 2019

Epigenetics & Chromatin

243

179

View full text Add to dashboard Cite

The histone variant H2A.Z is involved in several processes such as transcriptional control, DNA repair, regulation of centromeric heterochromatin and, not surprisingly, is implicated in diseases such as cancer. Here, we review the recent developments on H2A.Z focusing on its role in transcriptional activation and repression. H2A.Z, as a replication-independent histone, has been studied in several model organisms and inducible mammalian model systems. Its loading machinery and several modifying enzymes have been recently identified, and some of the long-standing discrepancies in transcriptional activation and/or repression are about to be resolved. The buffering functions of H2A.Z, as supported by genome-wide localization and analyzed in several dynamic systems, are an excellent example of transcriptional control. Posttranslational modifications such as acetylation and ubiquitination of H2A.Z, as well as its specific binding partners, are in our view central players in the control of gene expression. Understanding the key-mechanisms in either turnover or stabilization of H2A.Z-containing nucleosomes as well as defining the H2A.Z interactome will pave the way for therapeutic applications in the future.

show abstract

Section: H2az At Enhancers and Promotersmentioning

confidence: 99%

The histone variant H2A.Z in gene regulation

Giaimo

Ferrante

Herchenröther

et al. 2019

Epigenetics & Chromatin

243

179

View full text Add to dashboard Cite

show abstract

“…H2A.Z has been shown to destabilize nucleosomes and is often found at active promoters and enhancers (Martire and Banaszynski 2020), which we also observed in our C1 cluster. The role of H2A.Z in closed chromatin is less clear, but H2A.Z occupancy seems to correlate with pioneer TF binding to nucleosome-occupied regions and has been suggested to act as a scaffold for binding of pioneer TFs and chromatin remodelers (Cauchy, Koch, and Andrau 2017;Subramanian, Fields, and Boyer 2015). Whether SOX9 requires destabilized nucleosomes for chromatin opening and activation of target enhancers remains undetermined, but the requirement for H2A.Z enrichment and motif presence is evident from our study.…”

Section: Discussionmentioning

confidence: 57%

SOX9 acts as a dynamic pioneer factor inducing stable changes in the chromatin landscape to reprogram endothelial cells

Fuglerud

Drissler

Lotto

et al. 2020

Preprint

View full text Add to dashboard Cite

The transcription factor SOX9 is expressed in multiple tissues during embryogenesis and directs developmental processes. SOX9 is activated upon epithelial-to-mesenchymal transition (EMT) and the closely related process, endothelial-to-mesenchymal transition (EndMT), but its role in regulating these processes is less clear. Both EMT and EndMT are fundamental processes in normal development and cancer progression. Here, we show that SOX9 expression alone is sufficient to activate mesenchymal enhancers and steer endothelial cells towards a mesenchymal fate. By genome-wide mapping of the chromatin landscape, we show that SOX9 acts as a pioneer transcription factor, having the ability to open the chromatin structure and increase enrichment of active histone marks at a specific subset of target enhancers with an associated SOX motif. SOX9 also displays widespread chromatin pausing that is not associated with SOX motifs. This leads to a switch in enhancer activity states resulting in activation of mesenchymal genes and concurrent suppression of endothelial genes to drive EndMT. Moreover, SOX9 induced widespread changes in chromatin states throughout the genome without SOX9 binding. Our study highlights the crucial developmental role of SOX9 and provides new insight into key molecular functions of SOX9 in regulating the chromatin landscape and mechanisms of EndMT.

show abstract

“…ChIP-seq analysis of OCT4 and SOX2 revealed that a large fraction of their binding sites (respectively 28.2% and 42%) was more occupied upon IAA treatment, in line with TOBIAS and chromatome analysis (Figure 5G and H). However, OCT4 was reported to bind H2A.Z nucleosomes 61 and to lose binding upon H2A.Z knockdown 5 . Accordingly, sites bound by OCT4 only lost binding upon H2A.Z swapping with H2A, in contrast to sites bound by both OCT4 and SOX2 (Figure S5F).…”

Section: Resultsmentioning

confidence: 99%

Mechanistic basis of gene regulation by SRCAP and H2A.Z

Tollenaere,

Ugur,

Deluz

et al. 2024

Preprint

View full text Add to dashboard Cite

SummaryA central problem in gene regulation is to discriminate gene regulatory functions of chromatin composition from the one of chromatin-modifying complexes. This question has been virtually unexplored in the context of the H2A.Z histone variant and its incorporation into nucleosomes by the Snf2 Related CREBBP Activator Protein (SRCAP) complex. Here we combine rapid SRCAP depletion, a SRCAP mutant lacking H2A.Z deposition activity, and quantitative genome-wide approaches to dissect how SRCAP and H2A.Z regulate transcription in pluripotent stem cells. We find that SRCAP exhibits essential H2A.Z-independent functions in preventing DNA binding of lineage-specific transcription factors at enhancers and stimulating transcription factor binding at promoters. In contrast, H2A.Z acts mainly as a transcriptional repressor that requires dynamic reloading by SRCAP throughout the cell cycle. Our study demonstrates how the SRCAP-H2A.Z axis broadly orchestrates transcription to promote self-renewal, inhibit differentiation, and maintain plasticity of pluripotent stem cells.

show abstract

Two possible modes of pioneering associated with combinations of H2A.Z and p300/CBP at nucleosome-occupied enhancers

Cited by 9 publications

References 26 publications

The histone variant H2A.Z in gene regulation

The histone variant H2A.Z in gene regulation

SOX9 acts as a dynamic pioneer factor inducing stable changes in the chromatin landscape to reprogram endothelial cells

Mechanistic basis of gene regulation by SRCAP and H2A.Z

Contact Info

Product

Resources

About