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| Status |
Public on Sep 06, 2023 |
| Title |
(ATAC-seq_and_ChIP-seq) Spic regulates one-carbon metabolism and histone methylation in ground-state pluripotency |
| Organism |
Mus musculus |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
|
| Summary |
Understanding mechanisms of epigenetic regulation in embryonic stem cells (ESCs) is of fundamental importance for stem cell and developmental biology. Here we identify Spic, a member of the ETS family of transcription factors, as a specific marker of ground state pluripotency. We show that Spic is rapidly induced in ESCs cultured with GSK3-, MEK-inhibitors and LIF (2iL), and in response to MEK/ERK inhibition. ChIP-seq analysis demonstrated that Spic binds to enhancer elements that are associated with pluripotency genes. Interaction proteomics and genomic profiling confirmed that SPIC interacts with NANOG and stabilizes its binding to chromatin in 2iL-ESCs. Additional gain of function and loss of function experiments revealed that Spic controls genes involved in one carbon (1C) metabolism, Bhmt, Bhmt2, and Dmgdh, and the flux of SAM-to-SAH in 2iL-ESCs. By maintaining low levels of SAM, Spic controls the level of H3K4me3 and H3R17me2 histone methylation in ground state ESCs. Our data highlight the role of uncharacterized axillary transcription factors that link cellular metabolism to epigenetic regulation in ground state pluripotency.
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| Overall design |
ATAC-seq and ChIP-seq of SPIC and NANOG in Spic-KO, -OE, and -WT mouse ESCs
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| Web link |
https://pubmed.ncbi.nlm.nih.gov/37595034/
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| |
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| Contributor(s) |
Mirzadeh Azad F, Struys EA, Wingert V, Hannibal LH, Mills K, Jansen J, Longley DG, Stunnenberg H, Atlasi Y |
| Citation(s) |
37595034 |
| |
| Submission date |
Jan 03, 2023 |
| Last update date |
Dec 08, 2023 |
| Contact name |
Yaser Atlasi |
| E-mail(s) |
y.atlasi@qub.ac.uk
|
| Organization name |
Queen's University Belfast
|
| Department |
patrick G Johnston Centre for Cancer research
|
| Street address |
Lisburn Road
|
| City |
Belfast |
| ZIP/Postal code |
BT9 7AE |
| Country |
United Kingdom |
| |
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| Platforms (1) |
| GPL17021 |
Illumina HiSeq 2500 (Mus musculus) |
|
| Samples (24)
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| This SubSeries is part of SuperSeries: |
| GSE222058 |
Spic regulates one-carbon metabolism and histone methylation in ground-state pluripotency |
|
| Relations |
| BioProject |
PRJNA917523 |
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