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HBO1 determines SMAD action in pluripotency and mesendoderm specification.
- Source :
-
Nucleic acids research [Nucleic Acids Res] 2024 May 22; Vol. 52 (9), pp. 4935-4949. - Publication Year :
- 2024
-
Abstract
- TGF-β signaling family plays an essential role to regulate fate decisions in pluripotency and lineage specification. How the action of TGF-β family signaling is intrinsically executed remains not fully elucidated. Here, we show that HBO1, a MYST histone acetyltransferase (HAT) is an essential cell intrinsic determinant for TGF-β signaling in human embryonic stem cells (hESCs). HBO1-/- hESCs fail to response to TGF-β signaling to maintain pluripotency and spontaneously differentiate into neuroectoderm. Moreover, HBO1 deficient hESCs show complete defect in mesendoderm specification in BMP4-triggered gastruloids or teratomas. Molecularly, HBO1 interacts with SMAD4 and co-binds the open chromatin labeled by H3K14ac and H3K4me3 in undifferentiated hESCs. Upon differentiation, HBO1/SMAD4 co-bind and maintain the mesoderm genes in BMP4-triggered mesoderm cells while lose chromatin occupancy in neural cells induced by dual-SMAD inhibition. Our data reveal an essential role of HBO1, a chromatin factor to determine the action of SMAD in both human pluripotency and mesendoderm specification.<br /> (© The Author(s) 2024. Published by Oxford University Press on behalf of Nucleic Acids Research.)
- Subjects :
- Humans
Bone Morphogenetic Protein 4 metabolism
Bone Morphogenetic Protein 4 genetics
Cell Line
Chromatin metabolism
Endoderm cytology
Endoderm metabolism
Histones metabolism
Human Embryonic Stem Cells metabolism
Human Embryonic Stem Cells cytology
Pluripotent Stem Cells metabolism
Pluripotent Stem Cells cytology
Transforming Growth Factor beta metabolism
Cell Differentiation
Histone Acetyltransferases metabolism
Histone Acetyltransferases genetics
Mesoderm metabolism
Mesoderm cytology
Signal Transduction
Smad4 Protein metabolism
Smad4 Protein genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1362-4962
- Volume :
- 52
- Issue :
- 9
- Database :
- MEDLINE
- Journal :
- Nucleic acids research
- Publication Type :
- Academic Journal
- Accession number :
- 38421638
- Full Text :
- https://doi.org/10.1093/nar/gkae158