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Series GSE161994 Query DataSets for GSE161994
Status Public on May 03, 2021
Title BAP1 constrains pervasive H2AK119ub1 to control the transcriptional potential of the genome [ATAC-seq]
Organisms Drosophila melanogaster; Mus musculus
Experiment type Genome binding/occupancy profiling by high throughput sequencing
Summary Histone-modifying systems play fundamental roles in gene regulation and the development of multicellular organisms. Histone modifications that are enriched at gene regulatory elements have been heavily studied, but the function of modifications found more broadly throughout the genome remains poorly understood. This is exemplified by histone H2A monoubiquitylation (H2AK119ub1), which is enriched at Polycomb-repressed gene promoters but also covers the genome at lower levels. Here, using inducible genetic perturbations and quantitative genomics, we found that the BAP1 deubiquitylase plays an essential role in constraining H2AK119ub1 throughout the genome. Removal of BAP1 leads to pervasive genome-wide accumulation of H2AK119ub1, which causes widespread reductions in gene expression. We show that elevated H2AK119ub1 preferentially counteracts Ser5 phosphorylation on the C-terminal domain of RNA polymerase II at gene regulatory elements and causes reductions in transcription and transcription-associated histone modifications. Furthermore, failure to constrain pervasive H2AK119ub1 compromises Polycomb complex occupancy at a subset of Polycomb target genes, which leads to their derepression, providing a potential molecular rationale for why the BAP1 ortholog in Drosophila has been characterized as a Polycomb group gene. Together, these observations reveal that the transcriptional potential of the genome can be modulated by regulating the levels of a pervasive histone modification.
Overall design Mouse embryonic stem cells in which BAP1 can be conditionally removed were profiled for chromatin accessibility using spike-in calibrated ATAC-seq.
Contributor(s) Fursova NA, Klose RJ
Citation(s) 33888563
Submission date Nov 23, 2020
Last update date May 20, 2021
Contact name Nadezda A Fursova
Organization name University of Oxford
Department Department of Biochemistry
Lab Klose lab
Street address South Parks Rd
City Oxford
ZIP/Postal code OX13QU
Country United Kingdom
Platforms (1)
GPL25537 Illumina NextSeq 500 (Drosophila melanogaster; Mus musculus)
Samples (16)
GSM4929435 Bap1flfl_ATACseq_UNT_rep1
GSM4929436 Bap1flfl_ATACseq_UNT_rep2
GSM4929437 Bap1flfl_ATACseq_UNT_rep3
This SubSeries is part of SuperSeries:
GSE161996 BAP1 constrains pervasive H2AK119ub1 to control the transcriptional potential of the genome.
BioProject PRJNA680292
SRA SRP293979

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Supplementary file Size Download File type/resource 182.5 Mb (ftp)(http) BW 784.1 Mb (ftp)(http) BW 179.8 Mb (ftp)(http) BW 549.3 Mb (ftp)(http) BW
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