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Cell Rep 2022 Jul 12;402:111038. doi: 10.1016/j.celrep.2022.111038.
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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: acvr1b admp amh bmp4 bmp7.1 bmpr1a cdh1 chrd.1 dazl dhrs3 dppa2 e2f4 epcam epha2 esrrb foxa2 foxd3 foxq1 fst fut4 gsc hmces hmga2 id2 id3 ifngr1 inhbb inhbc.1 irf1 kit klf2 klf3 klf4 klf5 lef1 lefty mix1 myc nodal nr6a1 pecam1 pitx2 pmepa1 ppp2cb rhoa rhpn2 sall4 shisa3 smad4 smad6 smad7 sox2 stat3 szl tbxt tcf3 tdgf1 tgfb1 tgfb2 tgfbr2 thbs2 tmem119 tmem63a zfp36
GO keywords: embryo development [+]
Antibodies: H2afx Ab3 Smad1 Ab9 Smad1/5 Ab1 Smad2 Ab11 Smad2/3 Ab2 hmces Ab1
Morpholinos: hmces MO1

Article Images: [+] show captions