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@ARTICLE{VegaSendino:289078,
author = {M. Vega-Sendino and F. F. Lüttmann and T. Olbrich and Y.
Chen and C. Kuenne and P. Stein and D. Tillo and G. I. Carey
and J. Zhong$^*$ and V. Savy and L. Radonova and T. Lu and
B. Saykali and K.-P. Kim and C. N. Domingo and L. Schüler
and S. Günther and M. Bentsen and D. Bosnakovski and H.
Schöler and M. Kyba and T. K. Maity and L. M. Jenkins and
M. Looso and C. J. Williams and J. Kim and S. Ruiz},
title = {{T}he homeobox transcription factor {DUXBL} controls exit
from totipotency.},
journal = {Nature genetics},
volume = {56},
number = {4},
issn = {1061-4036},
address = {London},
publisher = {Macmillan Publishers Limited, part of Springer Nature},
reportid = {DKFZ-2024-00578},
pages = {697-709},
year = {2024},
note = {2024 Apr;56(4):697-709},
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.},
cin = {B400},
ddc = {570},
cid = {I:(DE-He78)B400-20160331},
pnm = {312 - Funktionelle und strukturelle Genomforschung
(POF4-312)},
pid = {G:(DE-HGF)POF4-312},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:38509386},
doi = {10.1038/s41588-024-01692-z},
url = {https://inrepo02.dkfz.de/record/289078},
}