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| Status |
Public on Feb 03, 2020 |
| Title |
Pro-neuronal activity of Myod1 due to promiscuous binding [FLAG ChIP-seq] |
| Organism |
Mus musculus |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
Basic helix-loop-helix (bHLH) pioneer transcription factors Myod1 and Ascl1 are biochemically related but produce fundamentally different outcomes when expressed in fibroblasts: Myod1 produces muscle cells and Ascl1 induces neurons. Here, we sought to investigate the molecular mechanisms explaining the differential activity. Surprisingly, we found a large overlap in the overall binding patterns of Ascl1 and Myod1 in fibroblasts, with both transcription factors accessing both neuronal and myogenic targets. We also observed similar changes in chromatin accessibility and transcriptional activation. Yet, Myod1 predominantly induced a muscle program and Ascl1 a neuronal program. We found that differences in binding affinity at key targets resulted in largely distinct reprogramming outcomes. Accordingly, exchanging Myod1’s C-terminal protein-protein interacting domain and DNA-binding basic domain with those of Ascl1 induces an Ascl1-like binding and converts Myod1 into a pro-neuronal factor. Finally, we found that co-expression of Myod1 with the transcriptional repressor Myt1l inhibits induction of the muscle program and yields functional neuronal cells. Our findings are compatible with the notion that pioneer factor activity is associated with high-affinity protein-DNA and suggest that promiscuous binding of pioneer factors can induce unspecific lineage features which need to be kept in check by co-factor interactions.
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| Overall design |
FLAG ChIP-seq was performed 48hr post-dox induction on: MEF+rtTA (control), MEF+flagAscl1, MEF+flagMyod1, MEF+flagMyod1+Myt1l and MEF+flagMyod1(Ascl1-basic+C-term) domain swap.
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| Contributor(s) |
Lee QY, Mall M, Kareta MS, Wapinski OL, Li R, Chang HY, Wernig M |
| Citation(s) |
32231311 |
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| Submission date |
Feb 11, 2019 |
| Last update date |
Oct 15, 2020 |
| Contact name |
Qian Yi Lee |
| E-mail(s) |
qianyi@stanford.edu
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| Organization name |
Stanford University
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| Department |
Bioengineering
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| Lab |
Wernig Lab
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| Street address |
265 Campus Drive
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| City |
Stanford |
| State/province |
CA |
| ZIP/Postal code |
94305 |
| 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 (26)
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| GSM3598002 |
[ChIP-seq, FLAG] MEF flagAscl1 IP (rep1) |
| GSM3598003 |
[ChIP-seq, FLAG] MEF flagAscl1 IP (rep2) |
| GSM3598004 |
[ChIP-seq, FLAG] MEF flagAscl1 IP (rep3) |
| GSM3598005 |
[ChIP-seq, FLAG] MEF flagAscl1 input (rep1) |
| GSM3598006 |
[ChIP-seq, FLAG] MEF flagAscl1 input (rep2) |
| GSM3598007 |
[ChIP-seq, FLAG] MEF flagAscl1 input (rep3) |
| GSM3598008 |
[ChIP-seq, FLAG] MEF flagMyod1 IP (rep1) |
| GSM3598009 |
[ChIP-seq, FLAG] MEF flagMyod1 IP (rep2) |
| GSM3598010 |
[ChIP-seq, FLAG] MEF flagMyod1 IP (rep3) |
| GSM3598011 |
[ChIP-seq, FLAG] MEF flagMyod1 IP (rep4) |
| GSM3598012 |
[ChIP-seq, FLAG] MEF flagMyod1 input (rep1) |
| GSM3598013 |
[ChIP-seq, FLAG] MEF flagMyod1 input (rep2) |
| GSM3598014 |
[ChIP-seq, FLAG] MEF flagMyod1 input (rep3) |
| GSM3598015 |
[ChIP-seq, FLAG] MEF flagMyod1 input (rep4) |
| GSM3598016 |
[ChIP-seq, FLAG] MEF rtTA-control IP (rep1) |
| GSM3598017 |
[ChIP-seq, FLAG] MEF rtTA-control IP (rep2) |
| GSM3598018 |
[ChIP-seq, FLAG] MEF rtTA-control input (rep1) |
| GSM3598019 |
[ChIP-seq, FLAG] MEF rtTA-control input (rep2) |
| GSM3598020 |
[ChIP-seq, FLAG] MEF flagMyod1(Ascl1-Basic+C-term) IP (rep1) |
| GSM3598021 |
[ChIP-seq, FLAG] MEF flagMyod1(Ascl1-Basic+C-term) IP (rep2) |
| GSM3598022 |
[ChIP-seq, FLAG] MEF flagMyod1(Ascl1-Basic+C-term) input (rep1) |
| GSM3598023 |
[ChIP-seq, FLAG] MEF flagMyod1(Ascl1-Basic+C-term) input (rep2) |
| GSM3598024 |
[ChIP-seq, FLAG] MEF flagMyod1+Myt1l IP (rep1) |
| GSM3598025 |
[ChIP-seq, FLAG] MEF flagMyod1+Myt1l IP (rep2) |
| GSM3598026 |
[ChIP-seq, FLAG] MEF flagMyod1+Myt1l input (rep1) |
| GSM3598027 |
[ChIP-seq, FLAG] MEF flagMyod1+Myt1l input (rep2) |
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| This SubSeries is part of SuperSeries: |
| GSE126414 |
Pro-neuronal activity of Myod1 due to promiscuous binding |
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| Relations |
| BioProject |
PRJNA521791 |
| SRA |
SRP185584 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE126410_TGM_flagAscl1_A1allinput.idrpeaks.0.1.merged.bed.gz |
254.3 Kb |
(ftp)(http) |
BED |
| GSE126410_TGM_flagMyoD_MDallinput.idrpeaks.0.1.merged.bed.gz |
663.8 Kb |
(ftp)(http) |
BED |
| GSE126410_TGM_flagMyod+Myt1l_combinedinput.idrpeaks.0.1.merged.bed.gz |
38.9 Kb |
(ftp)(http) |
BED |
| GSE126410_TGM_flagMyod-A1-B-C_combinedinput.idrpeaks.0.1.merged.bed.gz |
37.7 Kb |
(ftp)(http) |
BED |
| GSE126410_TGM_rtTA_Rallinput.idrpeaks.0.1.merged.bed.gz |
13.8 Kb |
(ftp)(http) |
BED |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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