GSE115169
Nodal signaling maintains H3K18ac landscape to promote mesendodermal differentiation through TRIM33
The epigenome of a cell is established and maintained by chromatin modifiers and remodelers, which are recruited to the chromatin by specific transcription factors. In this report, we show that nodal cross-talks with the epigenome through TRIM33-H3K18ac to mediate mesendodermal genes expression. The chromatin accessibility at mesendodermal genes depends on TRIM33. Moreover, histone acetylation is essential for TRIM33 recruitment to many nodal target genes involved in mesendodermal differentiation. The distribution pattern of the H3K18ac mark changes from foci to expanded domains at the mesendodermal genes promoter during embryonic stem cells (ESCs) differentiation to embryoid bodies (EBs). This could be the cue to facilitate TRIM33 colocalized with Smad2/3 at chromatin in EBs but not in ESCs. TRIM33 interacts with the H3K18ac “writer” p300 dependent on nodal signaling, providing a positive feedback to promote activation of mesendodermal genes and association with HDAC1 plays a negative role in activation of mesendodermal genes. Overall design: ESCs were cultured on gelatin coated plates with 15% serum ESC culture medium  and d2.5 EBs were cultured on bacteria plates without gelatin with 15% serum ESC culture medium withdrawl LIF. TRIM33 WT or KO ESCs and d2.5 EBs were harvested for ATAC-seq; TRIM33 WT or KO d2.5 EBs treated with activin A (50 ng/ml, R&D Systems) for 2hs or SB431542 (10 µM, TOCRIS) for 1h were harvested for RNA-seq and TRIM33 WT ESCs were harvested for RNA-SEQ.E14 ESCs were harvested for H3K18ac ChIP-seq, E 14 d2.5 EBs treated with activin A (50 ng/ml, R&D Systems) for 2hs or SB431542 (10 µM, TOCRIS) for 1h were harvested for H3K18ac ChIP-seq and H3K27ac ChIP-seq.