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Series GSE93941 Query DataSets for GSE93941
Status Public on Jan 01, 2018
Title MLL2 conveys transcription-independent H3K4me3 in the oocyte
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Genome binding/occupancy profiling by high throughput sequencing
Methylation profiling by high throughput sequencing
Summary Trimethylation of histone 3 lysine 4 (H3K4me3) is classically thought of as a mark of active promoters and yet it occurs at untranscribed domains. Partial redundancy of H3K4 methyltransferases has made it difficult to delineate the mechanisms underlying genomic targeting of H3K4me3. The oocyte provides an attractive system to investigate this, because extensive acquisition of H3K4me3 occurs in a non-dividing cell and ablation of a single H3K4 methyltransferase, Mll2, prevents most H3K4me3. We developed low-input chromatin immunoprecipitation to interrogate promoter associated histone modifications H3K4me3, H3K27ac and H3K27me3 throughout oogenesis. In non-growing oocytes, H3K4me3 was restricted to transcriptionally active promoters, but as oogenesis progresses, H3K4me3 accumulates in a transcription-independent manner: targeted to broad inter-genic regions, putative enhancers, and transcriptionally silent H3K27me3-marked promoters. Consequently, thousands of bivalent domains are established during oogenesis. Ablation of Mll2 resulted in loss of transcription-independent H3K4me3, with limited effects on transcription-coupled H3K4me3 or gene expression. Deletion of Dnmt3a/b showed that DNA methylation protects regions from acquiring H3K4me3. Our findings show that there are two independent mechanisms of targeting H3K4me3 to genomic elements, with MLL2 recruited to unmethylated CpG-rich regions independently of transcription.
Overall design We first characterised histone modifications associated with transcriptional regulation (H3K4me3, H3K27ac, and H3K27me3) in oocytes by adapting an ultra-low input native ChIP (ULI-nChIP) sequencing method. This allowed us to obtain high-resolution chromatin maps throughout oogenesis, from non-growing oocytes (NGOs) to fully-grown germinal vesicle (GV) oocytes, and to compare these profiles to gene expression and DNA methylation. Furthermore, this has enabled the first molecular interrogation of H3K4me3 in the conditional Dnmt3a/b and Mll2 KO oocytes.
Contributor(s) Hanna C, Huang J, Kranz A, Stewart AF, Kelsey G
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Submission date Jan 23, 2017
Last update date Jul 25, 2021
Contact name Felix Krueger
Organization name Altos Labs
Department Bioinformatics
Street address Granta Park
City Cambridge
ZIP/Postal code CB21 6GP
Country United Kingdom
Platforms (3)
GPL13112 Illumina HiSeq 2000 (Mus musculus)
GPL16417 Illumina MiSeq (Mus musculus)
GPL17021 Illumina HiSeq 2500 (Mus musculus)
Samples (86)
GSM2465416 MLL2_KO_GV_oocyte_rep1
GSM2465417 MLL2_KO_GV_oocyte_rep2
GSM2465418 MLL2_KO_GV_oocyte_rep3
BioProject PRJNA362876
SRA SRP097617

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Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE93941_10_5_Domains_75_25_NoOverlap_NoGaps_NoInterm_NoSmall_NoGaps.txt.gz 1.2 Mb (ftp)(http) TXT
GSE93941_C57BL6_oocytes_2kb_running_RPM_nofilters.txt.gz 39.1 Mb (ftp)(http) TXT
GSE93941_Dnmt3DKO.WT_H3K4me3_Me.Unme.domains_RPM.txt.gz 1.7 Mb (ftp)(http) TXT
GSE93941_ESC_oocyte_technical_optimisation_2kb_running_RPM_nofilters.txt.gz 28.0 Mb (ftp)(http) TXT
GSE93941_ESC_oocyte_technicaloptimisation_2kbrunning_RPM_nofilters.txt.gz 28.1 Mb (ftp)(http) TXT 1.5 Mb (ftp)(http) ZIP 15.6 Mb (ftp)(http) ZIP
GSE93941_H3K4me3_Dnmt3abDKOvWT_groups_2kb_running_RPM_nofilters.txt.gz 18.6 Mb (ftp)(http) TXT
GSE93941_MLL2_KO_GV_oocyte_rep1.cov.txt.gz 165.9 Mb (ftp)(http) TXT
GSE93941_MLL2_KO_GV_oocyte_rep2.cov.txt.gz 159.1 Mb (ftp)(http) TXT
GSE93941_MLL2_KO_GV_oocyte_rep3.cov.txt.gz 154.0 Mb (ftp)(http) TXT
GSE93941_MLL2_WT_GV_oocyte_rep1.cov.txt.gz 179.6 Mb (ftp)(http) TXT
GSE93941_MLL2_WT_GV_oocyte_rep2.cov.txt.gz 172.5 Mb (ftp)(http) TXT
GSE93941_MLL2_WT_GV_oocyte_rep3.cov.txt.gz 173.8 Mb (ftp)(http) TXT
GSE93941_OocyteH3K27ac_H3K27acGVpeaks_RPMcorrlength.txt.gz 1.4 Mb (ftp)(http) TXT
GSE93941_Oocyte_H3K27ac_5kbrunning_RPM_nofilters.txt.gz 10.2 Mb (ftp)(http) TXT
GSE93941_RAW.tar 83.1 Mb (http)(custom) TAR (of TXT)
GSE93941_RNAseq_groups_oocyte_mRNA_norep_RPKM_corrDNAcont.txt.gz 728.9 Kb (ftp)(http) TXT
GSE93941_RNAseq_groups_oocytemRNA_norep_RPKM_corrDNAcont.txt.gz 728.7 Kb (ftp)(http) TXT
GSE93941_bed_files_combinations_GV.tar.gz 2.9 Mb (ftp)(http) TAR 5.5 Mb (ftp)(http) ZIP
GSE93941_growing_oocytes_H3K4me3_peaks_and_seedpeaks.tar.gz 7.4 Mb (ftp)(http) TAR
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