@article{d795ec819ff743ebabc0b026828dcfc7,
title = "Thymine DNA glycosylase regulates cell-cycle-driven p53 transcriptional control in pluripotent cells",
abstract = "Cell cycle progression is linked to transcriptome dynamics and variations in the response of pluripotent cells to differentiation cues, mostly through unknown determinants. Here, we characterized the cell-cycle-associated transcriptome and proteome of mouse embryonic stem cells (mESCs) in naive ground state. We found that the thymine DNA glycosylase (TDG) is a cell-cycle-regulated co-factor of the tumor suppressor p53. Furthermore, TDG and p53 co-bind ESC-specific cis-regulatory elements and thereby control transcription of p53-dependent genes during self-renewal. We determined that the dynamic expression of TDG is required to promote the cell-cycle-associated transcriptional heterogeneity. Moreover, we demonstrated that transient depletion of TDG influences cell fate decisions during the early differentiation of mESCs. Our findings reveal an unanticipated role of TDG in promoting molecular heterogeneity during the cell cycle and highlight the central role of protein dynamics for the temporal control of cell fate during development.",
keywords = "cardiomyocyte, cell cycle, cell fate, gene regulation, p53, pluripotency, proteomics, self-renewal, stem cells, Thymine DNA glycosylase",
author = "Sergi Aranda and Anna Alcaine-Colet and Cecilia Ballar{\'e} and Enrique Blanco and Ivano Mocavini and Aleksandra Sparavier and Pedro Viz{\'a}n and Eva Borr{\`a}s and Eduard Sabid{\'o} and {Di Croce}, Luciano",
note = "Funding Information: We thank members of the Di Croce laboratory for critical reading of the manuscript and insightful discussions, V.A. Raker for scientific editing, and the CRG Genomics Unit, the CRG/UPF Flow Cytometry Unit, and the CRG Advanced Light Microscopy Unit for assistance with genomic sequencing, FACS, and microscopy services, respectively. The CRG/UPF Proteomics Unit is part of the Spanish Infrastructure for Omics Technologies (ICTS OmicsTech) and is a member of the ProteoRed PRB3 consortium, which is supported by grant PT17/0019 of the PE I+D+I 2013–2016 from the Instituto de Salud Carlos III (ISCIII), ERDF , and “ Secretaria d{\textquoteright}Universitats i Recerca del Departament d{\textquoteright}Economia i Coneixement de la Generalitat de Catalunya ” ( 2017SGR595 ). We acknowledge funding from Spanish Ministry of Economy, Industry, and Competitiveness (MEIC) ( BFU2016-75008-P and PID2019-108322GB-100 ), “ Fundaci{\'o}n Vencer El Cancer ” (VEC), and the European Regional Development Fund (FEDER) and from AGAUR to L.D.C. We acknowledge funding from The Ramon y Cajal program of the Ministerio de Ciencia, Innovaci{\'o}n y Universidades, and the European Social Fund under the reference number RYC-2018-025002-I and the Instituto de Salud Carlos III-FEDER ( PI19/01814 and PI22/01837 ) to S.A. We acknowledge the funding support from the Spanish Ministry of Science and Innovation to the EMBL partnership, the Centro de Excelencia Severo Ochoa , and the CERCA Programme/Generalitat de Catalunya . Publisher Copyright: {\textcopyright} 2023 Elsevier Inc.",
year = "2023",
month = aug,
day = "3",
doi = "10.1016/j.molcel.2023.07.003",
language = "English",
volume = "83",
pages = "2673--2691.e7",
journal = "Molecular Cell",
issn = "1097-2765",
publisher = "Cell Press",
number = "15",
}