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| 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.
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| 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.
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| Contributor(s) |
Hanna C, Huang J, Kranz A, Stewart AF, Kelsey G |
| Citation missing |
Has this study been published? Please login to update or notify GEO. |
| Submission date |
Jan 23, 2017 |
| Last update date |
Jul 25, 2021 |
| Contact name |
Felix Krueger |
| E-mail(s) |
fkrueger@altoslabs.com
|
| Organization name |
Altos Labs
|
| Department |
Bioinformatics
|
| Street address |
Granta Park
|
| City |
Cambridge |
| ZIP/Postal code |
CB21 6GP |
| Country |
United Kingdom |
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| Platforms (3) |
| GPL13112 |
Illumina HiSeq 2000 (Mus musculus) |
| GPL16417 |
Illumina MiSeq (Mus musculus) |
| GPL17021 |
Illumina HiSeq 2500 (Mus musculus) |
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| Samples (86)
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| Relations |
| BioProject |
PRJNA362876 |
| SRA |
SRP097617 |
| 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 |
| GSE93941_Epiblast_combinations_and_peaks.zip.gz |
1.5 Mb |
(ftp)(http) |
ZIP |
| GSE93941_GO_and_Mll2_peaks.zip.gz |
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 |
| GSE93941_bivalency_PGC_d05_d25_domains.zip.gz |
5.5 Mb |
(ftp)(http) |
ZIP |
| GSE93941_growing_oocytes_H3K4me3_peaks_and_seedpeaks.tar.gz |
7.4 Mb |
(ftp)(http) |
TAR |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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