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| Status |
Public on Jul 01, 2018 |
| Title |
Gas41 links histone acetylation to H2A.Z deposition and stem cell identity maintenance |
| Organism |
Mus musculus |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
Expression profiling by high throughput sequencing
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| Summary |
The histone variant H2A.Z is essential for maintaining the identity of embryonic stem cell (ESC) by keeping bivalent developmental genes at a poised state. However, how H2A.Z is deposited into the bivalent domains remains unknown. In mammals, two chromatin-remodeling complexes, Tip60/p400 and SRCAP, exchange the canonical histone H2A for H2A.Z in the chromatin. Here we show that Glioma Amplified Sequence 41 (Gas41), a shared subunit of the two H2A.Z-depositing complexes, functions as a reader of histone acetylation and recruits Tip60/p400 and SRCAP to deposit H2A.Z into specific chromatin regions including bivalent domains. The YEATS domain of Gas41 bound to acetylation on histone H3K27 and H3K14 both in vitro and in cells. Crystal structure of the Gas41 YEATS domain in complex with the H3K27ac peptide revealed that, similar to the AF9 and ENL YEATS domains, Gas41 YEATS forms a serine-lined aromatic cage for Kac recognition; mutations of either the aromatic residues of YEATS domain or the nearby residue of H3K27 abrogated the interaction. In mESCs, knockdown of Gas41 led to cell differentiation as the result of derepression of differentiation genes. Importantly, the differentiated morphology was rescued by expressing wild type Gas41, but not the YEATS domain mutated counterparts that do not recognize histone acetylation. Mechanically, we found that Gas41 depletion led to reduction of H2A.Z levels and a concomitant reduction of H3K27me3 levels at the promoters of a subset of bivalent genes. Together, our study identifies the Gas41 YEATS domain as a reader of histone acetylation and establishes a link between histone acetylation and H2A.Z deposition in the maintenance of ESC identity.
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| Overall design |
ChIP-seq of H2AZ, H3K27Ac, H3K27me3, H3K4me3, H3K14ac, were applied in J1 mouse ES cells; mRNA-seq of shNT and shGas41 in J1 mouse ES cells.
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| Contributor(s) |
Shi J, Hsu C, Shi X |
| Citation(s) |
29900004 |
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| Submission date |
Jun 26, 2017 |
| Last update date |
Jul 25, 2021 |
| Contact name |
Jiejun Shi |
| E-mail(s) |
jiejuns@uci.edu
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| Organization name |
University of California Irvine
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| Department |
School of Medicine
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| Lab |
Li lab
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| Street address |
5270 California Ave
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| City |
Irvine |
| State/province |
CA |
| ZIP/Postal code |
92617 |
| Country |
USA |
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| Platforms (1) |
| GPL13112 |
Illumina HiSeq 2000 (Mus musculus) |
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| Samples (27)
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| Relations |
| BioProject |
PRJNA391896 |
| SRA |
SRP110498 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE100460_RAW.tar |
7.0 Gb |
(http)(custom) |
TAR (of BW) |
| GSE100460_edgeR_shCon_EB_Day6_vs_shCon_EB_Day0.tsv.gz |
509.9 Kb |
(ftp)(http) |
TSV |
| GSE100460_edgeR_shGas41-1_vs_shCon.tsv.gz |
591.4 Kb |
(ftp)(http) |
TSV |
| GSE100460_edgeR_shGas41-2_vs_shCon.tsv.gz |
538.3 Kb |
(ftp)(http) |
TSV |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
| Processed data are available on Series record |
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