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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Mar 25, 2014 |
| Title |
CG hypomethylation in Lsh-/- mouse embryonic fibroblasts is associated with de novo H3K4me1 formation and altered cellular plasticity |
| Organism |
Mus musculus |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
Methylation profiling by high throughput sequencing
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| Summary |
DNA methylation patterns are established in early embryogenesis and are critical for cellular differentiation. To investigate the role of CG methylation in potential enhancer formation, we assessed H3K4me1 modification in murine embryonic fibroblasts (MEFs) derived from the DNA methylation mutant Lsh(-/-) mice. We report here de novo formation of putative enhancer elements at CG hypomethylated sites that can be dynamically altered. We found a subset of differentially enriched H3K4me1 regions clustered at neuronal lineage genes and overlapping with known cis-regulatory elements present in brain tissue. Reprogramming of Lsh(-/-) MEFs into induced pluripotent stem (iPS) cells leads to increased neuronal lineage gene expression of premarked genes and enhanced differentiation potential of Lsh(-/-) iPS cells toward the neuronal lineage pathway compared with WT iPS cells in vitro and in vivo. The state of CG hypomethylation and H3K4me1 enrichment is partially maintained in Lsh(-/-) iPS cells. The acquisition of H3K27ac and activity of subcloned fragments in an enhancer reporter assay indicate functional activity of several of de novo H3K4me1-marked sequences. Our results suggest a functional link of H3K4me1 enrichment at CG hypomethylated sites, enhancer formation, and cellular plasticity.
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| Overall design |
[ChIP-Seq] Genome-wide maps of H3K4me1 in Lsh WT and KO primary MEFs.
We report here differentiated enrichment of H3K4me1 at Lsh WT and KO mouse embryonic fibroblasts (MEFs). We found a subset of differentially enriched H3K4me1 regions in Lsh KO MEFs, and they clustered at neuronal lineage genes and overlapping with known cis-regulatory elements present in brain tissue. Reprogramming of Lsh-/- MEFs into induced pluripotent stem (iPS) cells leads to increased neuronal lineage gene expression of premarked genes and enhanced differentiation potential of Lsh-/- iPS cells toward the neuronal lineage pathway compared with WT iPS cells in vitro and in vivo. The state of H3K4me1 enrichment is partially maintained in Lsh-/- iPS cells, suggesting the regions are preserved as potential enhancers.
[MethylC-Seq] MethylC-Seq from Mus musculus primary MEFs.
Whole-genome single-base resolution methylcytosine map reveals profound changes that occur after Lsh deletion during embryonic development in primary WT and Lsh-/- MEFs. Lsh deletion leads to widespread decreases of CG methylation level at uniquely mapped genomic regions compared to wild type, including TSSs at protein-coding genes, and non-coding RNA genes.
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| Contributor(s) |
Yu W, McIntosh C, Lister R, Zhu I, Han Y, Ren J, Landsman D, Lee E, Briones V, Terashima M, Leighty R, Ecker JR, Muegge K |
| Citation(s) |
24711395, 25170028 |
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| Submission date |
Mar 24, 2014 |
| Last update date |
May 15, 2019 |
| Contact name |
Scott Durum |
| E-mail(s) |
durums@mail.nih.gov
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| Phone |
3018461545
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| Organization name |
National Cancer Institute
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| Department |
CCR
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| Lab |
Cancer Innovation Labratory
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| Street address |
Building 560, Room 31-71
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| City |
Frederick |
| State/province |
MD |
| ZIP/Postal code |
21702-1201 |
| Country |
USA |
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| Platforms (2) |
| GPL11002 |
Illumina Genome Analyzer IIx (Mus musculus) |
| GPL13112 |
Illumina HiSeq 2000 (Mus musculus) |
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| Samples (7)
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| Relations |
| BioProject |
PRJNA242559 |
| SRA |
SRP040524 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE56151_RAW.tar |
532.7 Mb |
(http)(custom) |
TAR (of TXT) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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