H3K18ac primes mesendodermal differentiation upon nodal signaling Journal Article
| Authors: | Luo, M.; Bai, J.; Liu, B.; Yan, P.; Zuo, F.; Sun, H.; Sun, Y.; Xu, X.; Song, Z.; Yang, Y.; Massagué, J.; Lan, X.; Lu, Z.; Chen, Y. G.; Deng, H.; Xie, W.; Xi, Q. |
| Article Title: | H3K18ac primes mesendodermal differentiation upon nodal signaling |
| Abstract: | 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. © 2019 The Author(s) Xi and colleagues explored how nodal signaling crosstalks with epigenome to specifically promote mesendodermal differentiation. They showed that TRIM33 specifically regulates the expression of a group of mesendodermal genes upon nodal signaling by maintaining the H3K18ac mark, and that HDAC1 and p300 are the key factors linking epigenome to the cell context-dependent nature of nodal responses during mesendodermal differentiation. © 2019 The Author(s) |
| Keywords: | controlled study; unclassified drug; promoter region; nonhuman; protein localization; animal cell; mouse; animal tissue; complex formation; gene expression; smad2 protein; smad3 protein; smad7 protein; transforming growth factor beta; embryo; embryonic stem cell; transcription initiation; cell protein; embryo development; cell differentiation; gene activation; messenger rna; epigenetics; chromatin immunoprecipitation; histone h3; embryonic stem cells; transcription factor pax6; nestin; wnt protein; mesoderm; rna polymerase ii; lysine; marker gene; endoderm; mouse embryo; fibroblast growth factor 8; enhancer region; histone deacetylase 1; histone deacetylase 2; wnt signaling; e1a associated p300 protein; antigen antibody complex; primitive streak; histone modification; gene ontology; histone acetyltransferase; histone acetylation; embryoid body; activin; chromatin accessibility; priority journal; article; nodal signaling; tgf beta signaling; mesendodermal differentiation; trim33; eomes protein; histone h3k18ac; nodal signaling protein; trim33 protein; gsc gene; mixl1 gene |
| Journal Title: | Stem Cell Reports |
| Volume: | 13 |
| Issue: | 4 |
| ISSN: | 2213-6711 |
| Publisher: | Cell Press |
| Date Published: | 2019-10-08 |
| Start Page: | 642 |
| End Page: | 656 |
| Language: | English |
| DOI: | 10.1016/j.stemcr.2019.08.016 |
| PUBMED: | 31564646 |
| PROVIDER: | scopus |
| PMCID: | PMC6830056 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 1 November 2019 -- Source: Scopus |
