THAP1: Role in Mouse Embryonic Stem Cell Survival and Differentiation

Overview

Journal Stem Cell Reports

Publisher Cell Press

Specialty Cell Biology

Date 2017 Jun 6

PMID 28579396

Citations 15

Authors

Francesca Aguilo

Zuchra Zakirova

Katie Nolan

Ryan Wagner

Rajal Sharma

Megan Hogan

Chengguo Wei

Yifei Sun

Martin J Walsh

Kevin Kelley

Weijia Zhang

Laurie J Ozelius

Pedro Gonzalez-Alegre

Thomas P Zwaka

Michelle E Ehrlich

Affiliations

Soon will be listed here.

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.

Citing Articles

The DYT6 dystonia causative protein THAP1 is responsible for proteasome activity via PSMB5 transcriptional regulation.

Wang Y, Wang Y, Iriki T, Hashimoto E, Inami M, Hashimoto S Nat Commun. 2025; 16(1):1600.

PMID: 39952963 PMC: 11828994. DOI: 10.1038/s41467-025-56867-x.

Loss-of-function mutations in the dystonia gene THAP1 impair proteasome function by inhibiting PSMB5 expression.

Ramage D, Grant D, Timms R Nat Commun. 2025; 16(1):1511.

PMID: 39929834 PMC: 11811203. DOI: 10.1038/s41467-025-56782-1.

Emerging role of a systems biology approach to elucidate factors of reduced penetrance: transcriptional changes in -linked dystonia as an example.

Diaw S, Ott F, Munchau A, Lohmann K, Busch H Med Genet. 2024; 34(2):131-141.

PMID: 38835919 PMC: 11006298. DOI: 10.1515/medgen-2022-2126.

Transcriptional regulatory network for neuron-glia interactions and its implication for DYT6 dystonia.

Yellajoshyula D Dystonia. 2024; 2.

PMID: 38737544 PMC: 11087070. DOI: 10.3389/dyst.2023.11796.

Circular RNA testis-expressed 14 overexpression induces apoptosis and suppresses migration of ox-LDL-stimulated vascular smooth muscle cells via regulating the microRNA 6509-3p/thanatos-associated domain-containing apoptosis-associated protein 1 axis.

Kou L, Yang N, Dong B, Yang J, Song Y, Li Y Bioengineered. 2022; 13(5):13150-13161.

PMID: 35635088 PMC: 9275967. DOI: 10.1080/21655979.2022.2070582.

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