RRC ID 69175
Author Hada M, Miura H, Tanigawa A, Matoba S, Inoue K, Ogonuki N, Hirose M, Watanabe N, Nakato R, Fujiki K, Hasegawa A, Sakashita A, Okae H, Miura K, Shikata D, Arima T, Shirahige K, Hiratani I, Ogura A.
Title Highly rigid H3.1/H3.2-H3K9me3 domains set a barrier for cell fate reprogramming in trophoblast stem cells.
Journal Genes Dev
Abstract The placenta is a highly evolved, specialized organ in mammals. It differs from other organs in that it functions only for fetal maintenance during gestation. Therefore, there must be intrinsic mechanisms that guarantee its unique functions. To address this question, we comprehensively analyzed epigenomic features of mouse trophoblast stem cells (TSCs). Our genome-wide, high-throughput analyses revealed that the TSC genome contains large-scale (>1-Mb) rigid heterochromatin architectures with a high degree of histone H3.1/3.2-H3K9me3 accumulation, which we termed TSC-defined highly heterochromatinized domains (THDs). Importantly, depletion of THDs by knockdown of CAF1, an H3.1/3.2 chaperone, resulted in down-regulation of TSC markers, such as Cdx2 and Elf5, and up-regulation of the pluripotent marker Oct3/4, indicating that THDs maintain the trophoblastic nature of TSCs. Furthermore, our nuclear transfer technique revealed that THDs are highly resistant to genomic reprogramming. However, when H3K9me3 was removed, the TSC genome was fully reprogrammed, giving rise to the first TSC cloned offspring. Interestingly, THD-like domains are also present in mouse and human placental cells in vivo, but not in other cell types. Thus, THDs are genomic architectures uniquely developed in placental lineage cells, which serve to protect them from fate reprogramming to stably maintain placental function.
Volume 36(1-2)
Pages 84-102
Published 2022-1-1
DOI 10.1101/gad.348782.121
PII gad.348782.121
PMID 34992147
PMC PMC8763053
MeSH Animals Cell Differentiation / genetics Female Histones* / genetics Histones* / metabolism Mammals Mice Placenta Pregnancy Stem Cells Trophoblasts* / metabolism
IF 9.527
Mice RBRC00639
DNA material CS-RfA-EVBsd (RDB06090) pENTR4-H1tetOx1 (RDB07916) pCMV-VSV-G-RSV-Rev (RDB04393) pCAG-HIVgp (RDB04394)
Human and Animal Cells 293T(RCB2202)