H3K18ac Primes Mesendodermal Differentiation upon Nodal Signaling.
IF: 7.294
Cited by: 10


Cellular responses to transforming growth factor β (TGF-β) depend on cell context. Here, we explored how TGF-β/nodal signaling crosstalks with the epigenome to promote mesendodermal differentiation. We find that expression of a group of mesendodermal genes depends on both TRIM33 and nodal signaling in embryoid bodies (EBs) but not in embryonic stem cells (ESCs). Only in EBs, TRIM33 binds these genes in the presence of expanded H3K18ac marks. Furthermore, the H3K18ac landscape at mesendodermal genes promotes TRIM33 recruitment. We reveal that HDAC1 binds to active gene promoters and interferes with TRIM33 recruitment to mesendodermal gene promoters. However, the TRIM33-interacting protein p300 deposits H3K18ac and further enhances TRIM33 recruitment. ATAC-seq data demonstrate that TRIM33 primes mesendodermal genes for activation by maintaining chromatin accessibility at their regulatory regions. Altogether, our study suggests that HDAC1 and p300 are key factors linking the epigenome through TRIM33 to the cell context-dependent nodal response during mesendodermal differentiation.


Gene Expression
chromatin accessibility
embryonic stem cells
histone acetylation
mesendodermal differentiation
nodal signaling

MeSH terms

Cell Differentiation
Embryonic Stem Cells
Gene Expression Regulation, Developmental
Nodal Protein
Promoter Regions, Genetic
Protein Binding
Protein Transport
Signal Transduction
Smad2 Protein
Smad3 Protein
Transcription Factors
p300-CBP Transcription Factors


Luo, Maoguo
Bai, Jianbo
Liu, Bofeng
Yan, Peiqiang
Zuo, Feifei
Sun, Hongyao
Sun, Ye
Xu, Xuanhao
Song, Zhihong
Yang, Yang
Massagué, Joan
Lan, Xun
Lu, Zhi
Chen, Ye-Guang
Deng, Haiteng
Xie, Wei
Xi, Qiaoran

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