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Series GSE111283 Query DataSets for GSE111283
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.
Overall design MethylC-seq of direct reprogramming from fibroblast to neuron
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
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
Platforms (1)
GPL17021 Illumina HiSeq 2500 (Mus musculus)
Samples (18)
GSM3027831 MethylC-seq_MEF_A
GSM3027832 MethylC-seq_MEF_B
GSM3027833 MethylC-seq_Ascl1_2d_A
BioProject PRJNA436411
SRA SRP133698

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Supplementary file Size Download File type/resource
GSE111283_RAW.tar 60.4 Gb (http)(custom) TAR (of TAR)
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Raw data are available in SRA
Processed data provided as supplementary file

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