000 03048 am a22004093u 4500
042 _adc
100 1 0 _aLin, Xionghui
_eauthor
_91154
700 1 0 _aSwedlund, Benjamin
_eauthor
_91155
700 1 0 _aTon, Mai-Linh N.
_eauthor
_91156
700 1 0 _aGhazanfar, Shila
_eauthor
_91157
700 1 0 _aGuibentif, Carolina
_eauthor
_91158
700 1 0 _aPaulissen, Catherine
_eauthor
_91159
700 1 0 _aBaudelet, Elodie
_eauthor
_91160
700 1 0 _aPlaindoux, Elise
_eauthor
_91161
700 1 0 _aAchouri, Younes
_eauthor
_91162
700 1 0 _aCalonne, Emilie
_eauthor
_91163
700 1 0 _aDubois, Christine
_eauthor
_91164
700 1 0 _aMansfield, William
_eauthor
_91165
700 1 0 _aZaffran, Stéphane
_eauthor
_91166
700 1 0 _aMarioni, John C.
_eauthor
_91167
700 1 0 _aFuks, Francois
_eauthor
_91168
700 1 0 _aGöttgens, Berthold
_eauthor
_91169
700 1 0 _aLescroart, Fabienne
_eauthor
_91170
700 1 0 _aBlanpain, Cédric
_eauthor
_91171
245 0 0 _aMesp1 controls the chromatin and enhancer landscapes essential for spatiotemporal patterning of early cardiovascular progenitors
260 _c2022-07-01.
500 _a/pmc/articles/PMC7613098/
500 _a/pubmed/35817961
520 _aThe mammalian heart arises from various populations of Mesp1-expressing cardiovascular progenitors (CPs) that are specified during the early stages of gastrulation. Mesp1 is a transcription factor (TF) that acts as a master regulator of CP specification and differentiation. However, how Mesp1 regulates the chromatin landscape of nascent mesodermal cells to define the temporal and spatial patterning of the distinct populations of CPs remains unknown. Here, by combining ChIP-seq, RNA-seq and ATAC-seq during mouse pluripotent stem cell differentiation, we defined the dynamic remodelling of the chromatin landscape mediated by Mesp1. We identified different enhancers that are temporally regulated to erase the pluripotent state and specify the pools of CPs that mediate heart development. We identified Zic2 and Zic3 as essential cofactors that act with Mesp1 to regulate its TF activity at key mesodermal enhancers, thereby regulating the chromatin remodelling and gene expression associated with the specification of the different populations of CPs in vivo. Our study identifies the dynamics of the chromatin landscape and enhancer remodelling associated with temporal patterning of early mesodermal cells into the distinct populations of CPs that mediate heart development.
540 _a
540 _ahttps://www.springernature.com/gp/open-research/policies/accepted-manuscript-termsUsers may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: https://www.springernature.com/gp/open-research/policies/accepted-manuscript-terms.
546 _aen
690 _aArticle
655 7 _aText
_2local
786 0 _nNat Cell Biol
856 4 1 _uhttp://dx.doi.org/10.1038/s41556-022-00947-3
_zConnect to this object online.
999 _c1738
_d1738