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Status |
Public on Feb 02, 2017 |
Title |
Not All H3K4 methylations are Created Equal: Mll2/COMPASS Dependency in Primordial Germ Cell Specification |
Organism |
Mus musculus |
Experiment type |
Genome binding/occupancy profiling by high throughput sequencing Expression profiling by high throughput sequencing Other
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Summary |
The spatiotemporal regulation of gene expression is central for cell-lineage specification during embryonic development and is achieved through the combinatorial action of transcription factors/co-factors and the epigenetic states at cis-regulatory elements. Previously, we reported that Mll2 (KMT2B)/COMPASS is responsible for the implementation of H3K4me3 at promoters of bivalent genes. Here, we show that Mll2/COMPASS can also implements H3K4me3 at some of the non-TSS regulatory elements, a subset of which share epigenetic signatures of active enhancers. Our mechanistic studies reveal that the association of Mll2’s CXXC domain with CpG-rich regions plays an instrumental role for chromatin targeting and subsequent implementation of H3K4me3. Although Mll2/COMPASS is required for H3K4me3 implementation on thousands of sites, it appears to be essential for the expression of a subset of genes, including those functioning in the control of transcriptional programs during embryonic development, indicating that not all H3K4 trimethylations implemented by MLL2/COMPASS are functionally equivalent.
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Overall design |
Characterization of H3K4me3 and Mll2 occupancy by ChIP-seq in mouse embryonic stem cells and identifying their role in gene expression and during differentiation by RNA-seq studies. A high resolution 4C-seq experiments involving two restriction digests (HindIII and NlaIII) were performed to investigate the interaction bewteen promoters of Prdm1 and Prdm14 (viewponts) and cis-regulatory elements whose H3K4me3 is catalyzed by Mll2 in mouse embryonic stem cells.
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Contributor(s) |
Hu D, Gao X, Shilatifard A |
Citation(s) |
28157506 |
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Submission date |
Feb 26, 2016 |
Last update date |
May 15, 2019 |
Contact name |
Ali Shilatifard |
E-mail(s) |
ash@northwestern.edu
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Organization name |
Northwestern University Feinberg School of Medicine
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Department |
Department of Biochemistry and Molecular Genetics
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Lab |
Shilatifard Lab
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Street address |
320 E Superior St
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City |
Chicago |
State/province |
IL |
ZIP/Postal code |
60611 |
Country |
USA |
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Platforms (2) |
GPL17021 |
Illumina HiSeq 2500 (Mus musculus) |
GPL19057 |
Illumina NextSeq 500 (Mus musculus) |
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Samples (90)
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Relations |
BioProject |
PRJNA313293 |
SRA |
SRP070890 |