Chemically Sumoylated Histone H4 Stimulates Intranucleosomal Demethylation by the LSD1–CoREST Complex

Dhall, Abhinav; Weller, Caroline E.; Chu, Aurea M.; Shelton, Patrick M. M.; Chatterjee, Champak

doi:10.1021/acschembio.7b00716

Cited by 42 publications

(55 citation statements)

References 30 publications

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“…7). In mammalian cells, sumoylated histone H4, which is associated with gene repression, in nucleosomes activates LSD1 (lysine-specific demethylase1) by a mechanism dependent on the SUMO-interacting motif in CoREST (co-repressor for element 1 silencing transcription factor) 49 . LSD1 demethylates methylated histone H3K4 to downregulate gene expression.…”

Section: Discussionmentioning

confidence: 99%

The PHD finger of Arabidopsis SIZ1 recognizes trimethylated histone H3K4 mediating SIZ1 function and abiotic stress response

2020

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Arabidopsis SIZ1 encodes a SUMO E3 ligase to regulate abiotic and biotic stress responses. Among SIZ1 or mammalian PIAS orthologs, plant SIZ1 proteins contain the plant homeodomain (PHD) finger, a C 4 HC 3 zinc finger. Here, we investigated the importance of PHD of Arabidopsis SIZ1. The Pro SIZ1 ::SIZ1(ΔPHD):GFP was unable to complement growth retardation, ABA hypersensitivity, and the cold-sensitive phenotype of the siz1 mutant, but Pro SIZ1 ::SIZ1: GFP could. Substitution of C162S in the PHD finger was unable to complement the siz1 mutation. Tri-methylated histone H3K4 (H3K4me3) was recognized by PHD, not by PHD (C162S). WRKY70 was up-regulated in the siz1-2 mutant and H3K4me3 accumulated at high levels in the WRKY70 promoter. PHD interacts with ATX, which mediates methylation of histone, probably leading to suppression of ATX's function. These results suggest that the PHD finger of SIZ1 is important for recognition of the histone code and is required for SIZ1 function and transcriptional suppression.

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Section: Discussionmentioning

confidence: 99%

The PHD finger of Arabidopsis SIZ1 recognizes trimethylated histone H3K4 mediating SIZ1 function and abiotic stress response

2020

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“…On the other hand, our genome-wide study of Ulp2-chromatin association shows that Ulp2 is not localized to all genes (for example, Fig EV1B), nor is transcription of all genes altered in ulp2D cells. Histone sumoylation in metazoans has important roles in transcription through its interactions with other epigenetic marks, such as trimethylation of H3K9 and H4K20, LSD1-CoREST complex-mediated demethylation of H3K4, and histone deacetylation by HDAC1 in human cells (Shiio & Eisenman, 2003;Metzler-Guillemain et al, 2008;Dhall et al, 2017); however, genome-wide analyses of histone-specific sumoylation have not yet been performed. Future genome-wide chromatin studies in yeast that catalog fully those genes subject to histone sumoylation and Ulp2-dependent transcriptional regulation will be informative.…”

Section: I Jmentioning

confidence: 99%

The Ulp2 SUMO protease promotes transcription elongation through regulation of histone sumoylation

Ryu

Wilson-Eisele

et al. 2019

The EMBO Journal

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Many eukaryotic proteins are regulated by modification with the ubiquitin‐like protein small ubiquitin‐like modifier (SUMO). This linkage is reversed by SUMO proteases, of which there are two in Saccharomyces cerevisiae, Ulp1 and Ulp2. SUMO‐protein conjugation regulates transcription, but the roles of SUMO proteases in transcription remain unclear. We report that Ulp2 is recruited to transcriptionally active genes to control local polysumoylation. Mutant ulp2 cells show impaired association of RNA polymerase II (RNAPII) with, and diminished expression of, constitutively active genes and the inducible CUP1 gene. Ulp2 loss sensitizes cells to 6‐azauracil, a hallmark of transcriptional elongation defects. We also describe a novel chromatin regulatory mechanism whereby histone‐H2B ubiquitylation stimulates histone sumoylation, which in turn appears to inhibit nucleosome association of the Ctk1 kinase. Ctk1 phosphorylates serine‐2 (S2) in the RNAPII C‐terminal domain (CTD) and promotes transcript elongation. Removal of both ubiquitin and SUMO from histones is needed to overcome the impediment to S2 phosphorylation. These results suggest sequential ubiquitin‐histone and SUMO‐histone modifications recruit Ulp2, which removes polySUMO chains and promotes RNAPII transcription elongation.

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“…Recently, it was proposed that LCH also represses REST-independent genes in a SUMO-2/3 dependent manner that requires the SIM in CoREST (the Corepressor of REST) [59]. As both LCH and H4su are associated with transcriptional repression, Dhall et al tested their potential crosstalk by employing semisynthetic nucleosomes containing both wild-type H4su and H3K4me2 [61]. They discovered an ~2-fold stimulation of LSD1 activity by H4su, which was dependent upon the SIM in CoREST (Figure 4).…”

Section: Chasing the High-hanging Fruit: Biochemical Effects Of Histomentioning

confidence: 99%

Studies of biochemical crosstalk in chromatin with semisynthetic histones

Leonen

Upadhyay

Chatterjee

2018

Current Opinion in Chemical Biology

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Reversible post-translational modifications of histone proteins in eukaryotic chromatin are closely tied to gene function and cellular development. Specific combinations of histone modifications, or marks, are implicated in distinct DNA-templated processes mediated by a range of chromatin-associated enzymes that install, erase and interpret the histone code. Mechanistic studies of the precise biochemical relationship between sets of marks and their effects on chromatin function are significantly complicated by the dynamic nature and heterogeneity of marks in cellular chromatin. Protein semisynthesis is a chemical technique that enables the piecewise assembly of uniformly and site-specifically modified histones in quantities sufficient for biophysical and biochemical analyses. Recent pioneering efforts in semisynthesis have yielded access to histones site-specifically modified by entire proteins, such as ubiquitin (Ub) and the small ubiquitin-like modifier (SUMO). Herein, we highlight key studies of biochemical crosstalk involving Ub and SUMO in chromatin that were enabled by histone semisynthesis.

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Chemically Sumoylated Histone H4 Stimulates Intranucleosomal Demethylation by the LSD1–CoREST Complex

Cited by 42 publications

References 30 publications

The PHD finger of Arabidopsis SIZ1 recognizes trimethylated histone H3K4 mediating SIZ1 function and abiotic stress response

The PHD finger of Arabidopsis SIZ1 recognizes trimethylated histone H3K4 mediating SIZ1 function and abiotic stress response

The Ulp2 SUMO protease promotes transcription elongation through regulation of histone sumoylation

Studies of biochemical crosstalk in chromatin with semisynthetic histones

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