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Polycomb protein RYBP facilitates super-enhancer activity.
Mol Med
November 2024
Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, 510080, China.
Background: Polycomb proteins are conventionally known as global repressors in cell fate determination. However, recent observations have shown their involvement in transcriptional activation, the mechanisms of which need further investigation.
Methods: Herein, multiple data from ChIP-seq, RNA-seq and HiChIP before or after RYBP depletion in embryonic stem cell (ESC), epidermal progenitor (EPC) and mesodermal cell (MEC) were analyzed.
Evidence for dual roles of histone H3 lysine 4 in antagonizing Polycomb group function and promoting target gene expression.
Genes Dev
November 2024
Curriculum in Genetics and Molecular Biology, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA;
Tight control over cell identity gene expression is necessary for proper adult form and function. The opposing activities of Polycomb and trithorax complexes determine the on/off state of cell identity genes such as the Hox factors. Polycomb group complexes repress target genes, whereas trithorax group complexes are required for their expression.
View Article and Find Full Text PDFNUP98 fusion proteins and KMT2A-MENIN antagonize PRC1.1 to drive gene expression in AML.
Cell Rep
November 2024
Department of Pediatric Oncology, Dana-Farber Cancer Institute, and Division of Hematology/Oncology, Boston Children's Hospital, Boston, MA 02215, USA. Electronic address:
Control of stem cell-associated genes by Trithorax group (TrxG) and Polycomb group (PcG) proteins is frequently misregulated in cancer. In leukemia, oncogenic fusion proteins hijack the TrxG homolog KMT2A and disrupt PcG activity to maintain pro-leukemogenic gene expression, though the mechanisms by which oncofusion proteins antagonize PcG proteins remain unclear. Here, we define the relationship between NUP98 oncofusion proteins and the non-canonical polycomb repressive complex 1.
View Article and Find Full Text PDFTight control over cell identity gene expression is necessary for proper adult form and function. The opposing activities of Polycomb and trithorax complexes determine the ON/OFF state of targets like the Hox genes. Trithorax encodes a methyltransferase specific to histone H3 lysine-4 (H3K4).
View Article and Find Full Text PDFASXLs binding to the PHD2/3 fingers of MLL4 provides a mechanism for the recruitment of BAP1 to active enhancers.
Nat Commun
June 2024
Department of Pharmacology, University of Colorado School of Medicine, Aurora, CO, 80045, USA.
Article Synopsis
- MLL4 and MLL3 are proteins often mutated in cancer that modify histones, specifically monomethylating histone H3K4, and contain unexplored PHD finger domains.
- The PHD2 and PHD3 fingers of MLL4 and MLL3 interact with ASXL2, a component of the PR-DUB complex, which plays a role in regulating histone modifications.
- Analysis shows that the MLL3/4 and PR-DUB complexes work together in a way that relies on the binding of ASXL1/2, which is essential for recruiting the deubiquitinase BAP1 to active enhancers in embryonic stem cells.
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