|
| Status |
Public on Jan 14, 2019 |
| Title |
Global DNA methylation remodeling during direct reprogramming from fibroblast to neuron [MethylC-seq] |
| Organism |
Mus musculus |
| Experiment type |
Methylation profiling by high throughput sequencing
|
| Summary |
Direct reprogramming from fibroblasts to neurons induces widespread cellular and transcriptional reconfigurations. In this study, we characterized global epigenomic changes during direct reprogramming using whole-genome base-resolution DNA methylome (mC) sequencing. We found that the pioneer transcription factor Ascl1 alone is sufficient for inducing robust non-CG methylation (mCH) accumulation in reprogrammed cells, but co-expression of Brn2 and Mytl1 was required to establish a global mCH pattern reminiscent of mature cortical neurons. Ascl1 alone induced strong promoter CG methylation (mCG) of fibroblast specific genes, while BAM overexpression additionally targets a competing myogenic program and directs a more faithful conversion to neuronal cells. Ascl1 induces local demethylation at its binding sites. Surprisingly, co-expression with Brn2 and Mytl1 inhibited the ability of Ascl1 to induce demethylation, suggesting a contextual regulation of transcription factor - epigenome interaction. Finally, we found that de novo methylation by DNMT3A is required for efficient neuronal reprogramming.
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| |
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| Overall design |
MethylC-seq of direct reprogramming from fibroblast to neuron
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| |
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| Contributor(s) |
Luo C, Lee QY, Wapinski OL, Castanon R, Nery JR, Cullen SM, Goodell MA, Chang HY, Wernig M, Ecker JR |
| Citation(s) |
30644360 |
| |
| Submission date |
Feb 28, 2018 |
| Last update date |
Mar 21, 2019 |
| Contact name |
Joseph R Ecker |
| E-mail(s) |
ecker@salk.edu
|
| Phone |
8584534100
|
| Organization name |
HHMI-Salk-Institute
|
| Department |
Genomic Analysis Laboratory
|
| Lab |
Ecker lab
|
| Street address |
10010 North Torrey Pines Road
|
| City |
La Jolla |
| State/province |
CA |
| ZIP/Postal code |
92037 |
| Country |
USA |
| |
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| Platforms (1) |
| GPL17021 |
Illumina HiSeq 2500 (Mus musculus) |
|
| Samples (18)
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| Relations |
| BioProject |
PRJNA436411 |
| SRA |
SRP133698 |
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