MMTR/Dmap1 Sets the Stage for Early Lineage Commitment of Embryonic Stem Cells by Crosstalk with PcG Proteins.

Abstract

Chromatin remodeling, including histone modification, chromatin (un)folding, and nucleosome remodeling, is a significant transcriptional regulation mechanism. By these epigenetic modifications, transcription factors and their regulators are recruited to the promoters of target genes, and thus gene expression is controlled through either transcriptional activation or repression. The Mat1-mediated transcriptional repressor (MMTR)/DNA methyltransferase 1 (DNMT1)-associated protein (Dmap1) is a transcription corepressor involved in chromatin remodeling, cell cycle regulation, DNA double-strand break repair, and tumor suppression. The Tip60-p400 complex proteins, including MMTR/Dmap1, interact with the oncogene Myc in embryonic stem cells (ESCs). These proteins interplay with the stem cell-related proteome networks and regulate gene expressions. However, the detailed mechanisms of their functions are unknown. Here, we show that MMTR/Dmap1, along with other Tip60-p400 complex proteins, bind the promoters of differentiation commitment genes in mouse ESCs. Hence, MMTR/Dmap1 controls gene expression alterations during differentiation. Furthermore, we propose a novel mechanism of MMTR/Dmap1 function in early stage lineage commitment of mouse ESCs by crosstalk with the polycomb group (PcG) proteins. The complex controls histone mark bivalency and transcriptional poising of commitment genes. Taken together, our comprehensive findings will help better understand the MMTR/Dmap1-mediated transcriptional regulation in ESCs and other cell types.

• Authors: Young Jin Lee, Seung Han Son, Chang Su Lim, Min Young Kim, Si Woo Lee, Sangwon Lee, Jinseon Jeon, Dae Hyun Ha, Na Rae Jung, Su Youne Han, Byung-Rok Do, Insung Na, Vladimir N Uversky, Chul Geun Kim
• Journal: Cells (Cells) Vol. 9 Issue 5 (05 11 2020) ISSN: 2073-4409 [Electronic] Switzerland
• PMID: 32403252 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• DNA-Binding Proteins
• Dmap1 protein, mouse
• Histones
• Polycomb-Group Proteins
• Repressor Proteins
• Suz12 protein, mouse
• Trans-Activators
• Polycomb Repressive Complex 2
• Kat5 protein, mouse
• Lysine Acetyltransferase 5
• DNA Helicases
• Ep400 protein, mouse
• Lysine

Topics

• Animals
• Cell Differentiation
• Cell Lineage
• Chromatin Assembly and Disassembly
• DNA Helicases (metabolism)
• DNA-Binding Proteins (metabolism)
• HEK293 Cells
• Histones (metabolism)
• Humans
• Lysine (metabolism)
• Lysine Acetyltransferase 5 (metabolism)
• Methylation
• Mice
• Mice, SCID
• Models, Biological
• Mouse Embryonic Stem Cells (cytology, metabolism)
• Polycomb Repressive Complex 2 (metabolism)
• Polycomb-Group Proteins (metabolism)
• Promoter Regions, Genetic
• Protein Binding
• Repressor Proteins (chemistry, metabolism)
• Trans-Activators (metabolism)