|
| Status |
Public on Apr 05, 2017 |
| Title |
The neuron-specific transcription factor Myt1l represses many non-neuronal fates |
| Organism |
Mus musculus |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
Expression profiling by high throughput sequencing
|
| Summary |
Normal differentiation and induced reprogramming require
the activation of target cell programs and silencing of donor cell
programs. In reprogramming, the same factors are often used to
reprogram many different donor cell types. As most developmental
repressors, such as RE1-silencing transcription factor (REST) and
Groucho (also known as TLE), are considered lineage-specific
repressors, it remains unclear how identical combinations of
transcription factors can silence so many different donor programs.
Distinct lineage repressors would have to be induced in different
donor cell types. Here we found that the pan neuron-specific
transcription factor Myt1-like (Myt1l) exerts its pro-neuronal
function by direct repression of many different somatic lineage
programs but not the neuronal program during reprogramming
and neurogenesis and in primary mouse neurons. The repressive
function of Myt1l is mediated by recruitment of a complex
containing Sin3b by binding to a previously uncharacterized
N-terminal domain. In agreement with its repressive function, the
genomic binding sites of Myt1l are similar in neurons and fibroblasts
and are preferentially in an open chromatin configuration. The
Notch signalling pathway is repressed by Myt1l through silencing
of several members, including Hes1. Acute knock-down of Myt1l
in the developing mouse brain mimicked a Notch gain-of-function
phenotype, suggesting that Myt1l allows newborn neurons to escape
Notch activation during normal development. Depletion of Myt1l in
primary postmitotic neurons de-repressed non-neuronal programs
and impaired neuronal gene expression and function, indicating
that many somatic lineage programs are actively and persistently
repressed by Myt1l to maintain neuronal identity. It is now tempting
to speculate that similar ‘many-but-one’ lineage repressors exist for
other cell fates; such repressors, in combination with lineage-specific
activators, would be prime candidates for use in reprogramming
additional cell types.
|
| |
|
| Overall design |
We utilized ChIP-seq of Myt1L, Sin3b, or HDAC1 in MEFs and the developing mouse brain to observe Myt1L chromatin localization and binding partner co-localization (31 samples). Additionally RNA-seq was performed to observe the consequence of Myt1L overexpression in MEFs or Myt1L knock-down in hippocampal neurons (10 samples).
|
| |
|
| Contributor(s) |
Wernig M, Mall M, Kareta M |
| Citation(s) |
28379941 |
| |
| Submission date |
Aug 17, 2015 |
| Last update date |
May 15, 2019 |
| Contact name |
Marius Wernig |
| Phone |
(650) 721-2495
|
| Organization name |
Stanford University
|
| Department |
Institute for Stem Cell Biology & Regenerative Medicine
|
| Street address |
265 Campus Drive, Rm. G3145
|
| City |
Stanford |
| State/province |
CA |
| ZIP/Postal code |
94305 |
| Country |
USA |
| |
|
| Platforms (1) |
| GPL17021 |
Illumina HiSeq 2500 (Mus musculus) |
|
| Samples (41)
|
|
| Relations |
| BioProject |
PRJNA293103 |
| SRA |
SRP062495 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE72121_13-5_Mouse_Brain_Myt1LB_cat.narrowPeak.gz |
19.6 Kb |
(ftp)(http) |
NARROWPEAK |
| GSE72121_48h_BAflM_Myt1LAB.narrowPeak.gz |
126.8 Kb |
(ftp)(http) |
NARROWPEAK |
| GSE72121_48h_BAtruncM_Myt1LAB.narrowPeak.gz |
29.0 Kb |
(ftp)(http) |
NARROWPEAK |
| GSE72121_48h_flM_HDAC1.narrowPeak.gz |
8.3 Kb |
(ftp)(http) |
NARROWPEAK |
| GSE72121_48h_flM_Myt1LB.narrowPeak.gz |
52.7 Kb |
(ftp)(http) |
NARROWPEAK |
| GSE72121_48h_flM_Sin3b.narrowPeak.gz |
42.2 Kb |
(ftp)(http) |
NARROWPEAK |
| GSE72121_48h_rtTA_Myt1LB.narrowPeak.gz |
370.2 Kb |
(ftp)(http) |
NARROWPEAK |
| GSE72121_48h_truncM_Myt1LB.narrowPeak.gz |
113.1 Kb |
(ftp)(http) |
NARROWPEAK |
| GSE72121_genes_Hippo.fpkm_tracking.gz |
1.6 Mb |
(ftp)(http) |
FPKM_TRACKING |
| GSE72121_genes_Monly.fpkm_tracking.gz |
4.2 Mb |
(ftp)(http) |
FPKM_TRACKING |
| GSE72121_macs2.con.13-5_Mouse_Brain_Myt1LB_cat_peaks.narrowPeak.gz |
38.1 Kb |
(ftp)(http) |
NARROWPEAK |
| GSE72121_macs2.con.48h_BAflM_Myt1LAB_cat_peaks.narrowPeak.gz |
104.0 Kb |
(ftp)(http) |
NARROWPEAK |
| GSE72121_macs2.con.48h_BAtruncM_Myt1LAB_cat_peaks.narrowPeak.gz |
41.9 Kb |
(ftp)(http) |
NARROWPEAK |
| GSE72121_macs2.con.48h_flM_HDAC1_cat_peaks.narrowPeak.gz |
11.5 Kb |
(ftp)(http) |
NARROWPEAK |
| GSE72121_macs2.con.48h_flM_Myt1LB_cat_peaks.narrowPeak.gz |
61.2 Kb |
(ftp)(http) |
NARROWPEAK |
| GSE72121_macs2.con.48h_flM_Sin3b_cat_peaks.narrowPeak.gz |
27.9 Kb |
(ftp)(http) |
NARROWPEAK |
| GSE72121_macs2.con.48h_truncM_Myt1LB_cat_peaks.narrowPeak.gz |
56.4 Kb |
(ftp)(http) |
NARROWPEAK |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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