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Cell Rep July 12, 2022; 40 (2): 111038.
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HMCES modulates the transcriptional regulation of nodal/activin and BMP signaling in mESCs.

Liang T , Bai J , Zhou W , Lin H , Ma S , Zhu X , Tao Q , Xi Q .

Despite the fundamental roles of TGF-β family signaling in cell fate determination in all metazoans, the mechanism by which these signals are spatially and temporally interpreted remains elusive. The cell-context-dependent function of TGF-β signaling largely relies on transcriptional regulation by SMAD proteins. Here, we discover that the DNA repair-related protein, HMCES, contributes to early development by maintaining nodal/activin- or BMP-signaling-regulated transcriptional network. HMCES binds with R-SMAD proteins, co-localizing at active histone marks. However, HMCES chromatin occupancy is independent on nodal/activin or BMP signaling. Mechanistically, HMCES competitively binds chromatin to limit binding by R-SMAD proteins, thereby forcing their dissociation and resulting in repression of their regulatory effects. In Xenopus laevis embryo, hmces KD causes dramatic development defects with abnormal left-right axis asymmetry along with increasing expression of lefty1. These findings reveal HMCES transcriptional regulatory function in the context of TGF-β family signaling.

PubMed ID: 35830803
Article link: Cell Rep

Species referenced: Xenopus laevis
Genes referenced: lefty