AI Article Synopsis
- THAP1 is a transcription factor that, when mutated, leads to dystonia, specifically DYT6, a movement disorder.
- The study reveals that normal THAP1 is crucial for maintaining embryonic stem cell survival, proliferation, and differentiation towards neuroectodermal tissues.
- Mutations or loss of THAP1 increase cell death and disrupt the regulation of essential genes involved in differentiation, indicating its role in gene expression regulation.
Article Abstract
THAP1 (THAP [Thanatos-associated protein] domain-containing, apoptosis-associated protein 1) is a ubiquitously expressed member of a family of transcription factors with highly conserved DNA-binding and protein-interacting regions. Mutations in THAP1 cause dystonia, DYT6, a neurologic movement disorder. THAP1 downstream targets and the mechanism via which it causes dystonia are largely unknown. Here, we show that wild-type THAP1 regulates embryonic stem cell (ESC) potential, survival, and proliferation. Our findings identify THAP1 as an essential factor underlying mouse ESC survival and to some extent, differentiation, particularly neuroectodermal. Loss of THAP1 or replacement with a disease-causing mutation results in an enhanced rate of cell death, prolongs Nanog, Prdm14, and/or Rex1 expression upon differentiation, and results in failure to upregulate ectodermal genes. ChIP-Seq reveals that these activities are likely due in part to indirect regulation of gene expression.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5511047 | PMC |
| http://dx.doi.org/10.1016/j.stemcr.2017.04.032 | DOI Listing |
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