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| Status |
Public on May 13, 2021 |
| Title |
The SAM domain-containing protein 1 (SAMD1) acts as a repressive chromatin regulator at unmethylated CpG islands |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
Genome binding/occupancy profiling by high throughput sequencing
|
| Summary |
CpG-islands (CGIs) are key regulatory DNA elements at most promoters, but how they influence the chromatin status and transcription remains elusive. Here we identify and characterize SAMD1 (SAM domain-containing protein 1) as an unmethylated CGI-binding protein. SAMD1 possesses an atypical winged-helix domain that directly recognizes unmethylated CpG-containing DNA via simultaneous interactions with both the major and the minor groove. The SAM domain interacts with L3MBTL3, but it can also homopolymerize into a closed pentameric ring. At a genome-wide level, SAMD1 localizes to H3K4me3-decorated CGIs, where it acts as a repressor. SAMD1 tethers L3MBTL3 to chromatin and interacts with the KDM1A histone demethylase complex to modulate H3K4me2 and H3K4me3 levels at CGIs, thereby providing a mechanism for SAMD1-mediated transcriptional repression. Absence of SAMD1 impairs ES cell differentiation processes, leading to miss-regulation of key biological pathways. Together, our work establishes SAMD1 as a novel chromatin regulator acting at unmethylated CGIs.
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| Overall design |
ChIP-Seq of SAMD1 (2x), L3MBTL3 (2x), KDM1A (2x), H3K4me2 (2x), H3K4me3 (2x), H3K27ac (1x), H3K27me3 (1x) in WT and SAMD1 knockout cells. RNA-Seq of WT and SAMD1 knockout cells (4x). RNA-Seq after 7 days of undirected differentiation (3x). RNA-Seq after KDM1A and L3MBTL3 KO (3x).
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| Contributor(s) |
Stielow B, Nist A, Liefke R |
| Citation(s) |
33980486, 36810619 |
| |
| Submission date |
Jan 28, 2020 |
| Last update date |
Mar 15, 2023 |
| Contact name |
Robert Liefke |
| E-mail(s) |
robert.liefke@imt.uni-marburg.de
|
| Organization name |
Philipps University of Marburg
|
| Department |
Institute of Molecular Biology and Tumor Research (IMT)
|
| Street address |
Hans-Meerwein-Str. 2
|
| City |
Marburg |
| State/province |
Hessen |
| ZIP/Postal code |
35043 |
| Country |
Germany |
| |
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| Platforms (2) |
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| Samples (55)
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|
| Relations |
| BioProject |
PRJNA603553 |
| SRA |
SRP245629 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE144396_DeSeq2-Differentiation-SAMD1KOvsWT.txt.gz |
621.0 Kb |
(ftp)(http) |
TXT |
| GSE144396_DeSeq2-KDM1AKOvsWT.txt.gz |
947.1 Kb |
(ftp)(http) |
TXT |
| GSE144396_DeSeq2-L3MBTL3KOvsWT.txt.gz |
957.1 Kb |
(ftp)(http) |
TXT |
| GSE144396_NormalizedCounts-Differentiation.txt.gz |
1.1 Mb |
(ftp)(http) |
TXT |
| GSE144396_NormalizedCounts-WT-KDM1AKO-L3MBTL3KO.txt.gz |
833.3 Kb |
(ftp)(http) |
TXT |
| GSE144396_RAW.tar |
6.8 Gb |
(http)(custom) |
TAR (of BW) |
| GSE144396_RNA-Seq_DeSeq2.txt.gz |
1.1 Mb |
(ftp)(http) |
TXT |
| GSE144396_RNA-Seq_NormalizedCounts.txt.gz |
1.1 Mb |
(ftp)(http) |
TXT |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
| Processed data are available on Series record |
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