Journal Article

DKFZ-2024-00578

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png The homeobox transcription factor DUXBL controls exit from totipotency.

Vega-Sendino, M. ; Lüttmann, F. F. ; Olbrich, T. ; Chen, Y. ; Kuenne, C. ; Stein, P. ; Tillo, D. ; Carey, G. I. ; Zhong, J.DKFZ* ; Savy, V. ; Radonova, L. ; Lu, T. ; Saykali, B. ; Kim, K.-P. ; Domingo, C. N. ; Schüler, L. ; Günther, S. ; Bentsen, M. ; Bosnakovski, D. ; Schöler, H. ; Kyba, M. ; Maity, T. K. ; Jenkins, L. M. ; Looso, M. ; Williams, C. J. ; Kim, J. ; Ruiz, S.

2024
Macmillan Publishers Limited, part of Springer Nature London

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Please use a persistent id in citations: doi:10.1038/s41588-024-01692-z

Abstract: In mice, exit from the totipotent two-cell (2C) stage embryo requires silencing of the 2C-associated transcriptional program. However, the molecular mechanisms involved in this process remain poorly understood. Here we demonstrate that the 2C-specific transcription factor double homeobox protein (DUX) mediates an essential negative feedback loop by inducing the expression of DUXBL to promote this silencing. We show that DUXBL gains accessibility to DUX-bound regions specifically upon DUX expression. Furthermore, we determine that DUXBL interacts with TRIM24 and TRIM33, members of the TRIM superfamily involved in gene silencing, and colocalizes with them in nuclear foci upon DUX expression. Importantly, DUXBL overexpression impairs 2C-associated transcription, whereas Duxbl inactivation in mouse embryonic stem cells increases DUX-dependent induction of the 2C-transcriptional program. Consequently, DUXBL deficiency in embryos results in sustained expression of 2C-associated transcripts leading to early developmental arrest. Our study identifies DUXBL as an essential regulator of totipotency exit enabling the first divergence of cell fates.

Note: 2024 Apr;56(4):697-709

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Contributing Institute(s):

1. NWG Hirngenom-Mosaizismus und Tumorgenese (B400)

Research Program(s):

1. 312 - Funktionelle und strukturelle Genomforschung (POF4-312) (POF4-312)

Appears in the scientific report 2024

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Database coverage:
; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; DEAL Nature ; Ebsco Academic Search ; Essential Science Indicators ; IF >= 30 ; JCR ; Nationallizenz ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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