DPY30 acts as an ASH2L-specific stabilizer to stimulate the enzyme activity of MLL family methyltransferases on different substrates

Zhao, Lijie; Huang, Naizhe; Mencius, Jun; Li, Yanjing; Xu, Ying; Zheng, Yongxin; He, Wei; Li, Na; Zheng, Jun; Zhuang, Min; Qin, Shu; Chen, Yong

doi:10.1016/j.isci.2022.104948

Cited by 5 publications

(3 citation statements)

References 52 publications

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“…1a ). 2 , 3 Therefore, to investigate the dynamics of genome-wide H3K4 methylation, we individually integrated the degradation tag FKBP12 F36V (dTAG) into the N-terminus of the endogenous Rbbp5 and Dpy30 loci in mouse embryonic stem cells (mESCs) to allow rapid disruption of COMPASS (Fig. 1a ; Supplementary information, Fig.…”

mentioning

confidence: 99%

H3K4me2/3 modulate the stability of RNA polymerase II pausing

Song

Peng

et al. 2023

Cell Res

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mentioning

confidence: 99%

H3K4me2/3 modulate the stability of RNA polymerase II pausing

Song

Peng

et al. 2023

Cell Res

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“…Although SET1A and SET1B in mammalian cells are mainly responsible for bulk H3K4me3, MLL1 and MLL2 catalyze H3K4me3 in a locus-specific manner and can partially compensate for SET1A/SET1B loss in H3K4me3 deposition ( 20 ). Among the four shared COMPASS subunits known as WRAD (WDR5, RBBP5, ASH2L, and DPY30), RBBP5 is essential for complex assembly, nucleosome recognition, and thus catalytic activation, whereas DPY30 flexibly associates with and stimulates H3K4 methylation ( 21, 58–65 ). Therefore, to investigate the dynamics of genome-wide H3K4 methylation, we established mRBBP5-dTAG and mDPY30 mESCs to individually degrade RBBP5 or DPY30 (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…Among the four shared COMPASS subunits known as WRAD (WDR5, RBBP5, ASH2L, and DPY30), RBBP5 is essential for complex assembly, nucleosome recognition, and thus catalytic activation, whereas DPY30 flexibly associates with and stimulates H3K4 methylation (21,(58)(59)(60)(61)(62)(63)(64)(65). Therefore, to investigate the dynamics of genome-wide H3K4 methylation, we established mRBBP5-dTAG and mDPY30 mESCs to individually degrade RBBP5 or DPY30 (Fig.…”

Section: Compass Continuously Maintains H3k4 Methylationmentioning

confidence: 99%

H3K4 di- and trimethylation modulate the stability of RNA polymerase II pausing

Song

Peng

et al. 2022

Preprint

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SUMMARYModifications of histones are intricately linked with the regulation of gene expression, with demonstrated roles in various physiological processes and disease pathogenesis. Methylation of histone H3 lysine 4 (H3K4), implemented by the COMPASS family, is enriched at promoters and associated cis-regulatory elements, with H3K4 trimethylation (H3K4me3) considered a hallmark of active gene promoters. However, the relative roles of deposition and removal of H3K4 methylation, as well as the extent to which these events contribute to transcriptional regulation have so far remained unclear. Here, through rapid depletion of the transcription regulator SPT5 or either of two shared subunits of COMPASS family members, we reveal a dynamic turnover of H3K4me3 mediated by the KDM5 family of histone demethylases. Loss of H3K4me3 following COMPASS disruption does not impair the recruitment of TFIID and initiating RNA polymerase II (Pol II). Instead, H3K4me3 loss leads to reductions in the paused form of Pol II on chromatin while inducing the relative enrichment of the Integrator-PP2A (INTAC) termination complex, leading to reduced levels of elongating polymerases, thus revealing how H3K4me3 dynamics can regulate Pol II pausing to sustain or attenuate transcription.

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Roles and Regulation of H3K4 Methylation During Mammalian Early Embryogenesis and Embryonic Stem Cell Differentiation

Terzi Çizmecioğlu

2024

Advances in Experimental Medicine and Biology

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DPY30 acts as an ASH2L-specific stabilizer to stimulate the enzyme activity of MLL family methyltransferases on different substrates

Cited by 5 publications

References 52 publications

H3K4me2/3 modulate the stability of RNA polymerase II pausing

H3K4me2/3 modulate the stability of RNA polymerase II pausing

H3K4 di- and trimethylation modulate the stability of RNA polymerase II pausing

Roles and Regulation of H3K4 Methylation During Mammalian Early Embryogenesis and Embryonic Stem Cell Differentiation

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