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Series GSE88745 Query DataSets for GSE88745
Status Public on Sep 05, 2017
Title A hyperdynamic H3.3 nucleosome marks promoter regions in pluripotent embryonic stem cells
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Genome binding/occupancy profiling by high throughput sequencing
Summary Histone variants and their chaperones are key regulators of eukaryotic transcription, and are critical for normal development. The histone variant H3.3 has been shown to play important roles in pluripotency and differentiation, and although its genome-wide patterns have been investigated, little is known about the role of its dynamic turnover in transcriptional regulation. To elucidate the role of H3.3 dynamics in embryonic stem cell (ESC) biology, we generated mouse ESC lines carrying a single copy of a doxycycline (Dox)-inducible HA-tagged version of H3.3, and monitored the rate of incorporation of the HA-tagged variant by ChIP-seq at varying time points following Dox induction. Active H3K4me3-enriched genes display high turnover dynamics in transcription start sites (TSS); H3K27me3-enriched genes have a lower turnover dynamics in the TSS, but higher turnover rates in gene bodies; developmental bivalent genes marked by both H3K4me3 and H3K27me3 show a mixed behavior with high TSS dynamics and high gene body dynamics, especially in genes bound by both PRC1 and PRC2. In contrast, genes proximal to super-enhancers show the most reduced gene-body turnover dynamics, while genes proximal to other enhancers show no unique pattern. In RA-treated cells, while the overall profile in expressed genes remains largely unaltered over the TSS and gene body, a significant and dramatic decrease in turnover occurs at the -1 nucleosome position immediately before the TSS, revealing a hyperdynamic nucleosome in promoters of genes expressed in ESCs. We suggest that histone turnover dynamics provides an additional mechanism involved in expression regulation, that gene-body turnover dynamics is distinct from that of promoter regions, and that a hyperdynamic -1 nucleosome marks promoters in ESCs. Our data provide evidence for regional regulation of H3.3 turnover in ESC promoters, and calls for testing, in high resolution, the dynamic behavior of additional histone variants and other structural chromatin proteins.
Overall design Examination of genome-wide H3.3 incorporation in mouse ESC.
Contributor(s) Schlesinger S, Melcer S, Kaplan T, Meshorer E
Citation(s) 29036702
Submission date Oct 14, 2016
Last update date May 15, 2019
Contact name Tommy Kaplan
Organization name Hebrew University
Department School of Computer Science and Engineering
Street address Givat Ram Campus
City Jerusalem
ZIP/Postal code 91904
Country Israel
Platforms (2)
GPL17021 Illumina HiSeq 2500 (Mus musculus)
GPL19057 Illumina NextSeq 500 (Mus musculus)
Samples (9)
GSM2345017 H3.3-HA ChIP-seq ES cells 1hr DOX
GSM2345018 H3.3-HA ChIP-seq ES cells 4hr DOX
GSM2345019 H3.3-HA ChIP-seq ES cells 8hr DOX
BioProject PRJNA348448
SRA SRP091548

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE88745_RAW.tar 670.0 Mb (http)(custom) TAR (of BIGWIG, FPKM_TRACKING)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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