CDYL1-dependent decrease in lysine crotonylation at DNA double-strand break sites functionally uncouples transcriptional silencing and repair

Abu‐Zhayia, Enas R; Bishara, Laila A; Machour, Feras E; Barisaac, Alma Sophia; Ben-Oz, Bella M; Ayoub, Nabieh

doi:10.1016/j.molcel.2022.03.031

Cited by 17 publications

(12 citation statements)

References 82 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…On the one hand, CDYL1 may achieve transcriptional repression by recruiting enhancers of zeste homolog 2 (EZH2) methyltransferase to DSB sites to promote local increases of the repressive methyl mark H3K27me3. On the other hand, CDYL1 can also downregulate Kcr at DSB sites via its crotonyl-CoA hydratase activity, resulting in the eviction of the transcription elongation factor ENL and transcriptional silencing [ 90 , 95 , 97 ]. Using ChIP-seq analysis, Enas R. Abu-Zhayia et al found that the decrease in the levels of H3K9cr at DSB sites was accompanied by CDYL1 enrichment [ 97 ].…”

Section: Histone Kcr Is a New Determinant Of Double-strand Break (Dsb...mentioning

confidence: 99%

“…On the other hand, CDYL1 can also downregulate Kcr at DSB sites via its crotonyl-CoA hydratase activity, resulting in the eviction of the transcription elongation factor ENL and transcriptional silencing [ 90 , 95 , 97 ]. Using ChIP-seq analysis, Enas R. Abu-Zhayia et al found that the decrease in the levels of H3K9cr at DSB sites was accompanied by CDYL1 enrichment [ 97 ]. The decrease in Kcr levels in CDYL1-deficient cells is significantly lower than the decrease observed in CDYL1-proficient cells at DSBs.…”

Section: Histone Kcr Is a New Determinant Of Double-strand Break (Dsb...mentioning

confidence: 99%

“…The decrease in Kcr levels in CDYL1-deficient cells is significantly lower than the decrease observed in CDYL1-proficient cells at DSBs. Crotonyl-CoA hydratase activity deficient mutant CDYL1-S467A was found to still promote DSB repair but lose the ability to promote Kcr downregulation and transcriptional repression at the DSB sites [ 97 ] ( Figure 1 ). These results provide the first detailed explanation of the molecular mechanism of CDYL1 by which CDYL1-dependent Kcr participates in DSB-induced transcriptional silencing and suggest that homologous recombination-mediated repair and DSB-induced transcription silencing may occur independently.…”

Section: Histone Kcr Is a New Determinant Of Double-strand Break (Dsb...mentioning

confidence: 99%

“…According to Enas R. Abu-Zhayia et al, CDYL1 does not affect HR-mediated DSB repair through its crotonyl-CoA hydratase activity. In other words, CDYL1 does not regulate HR by influencing Kcr of RPA1 through modulating intracellular crotonly-CoA [ 97 ]. Other regulatory mechanisms, such as HCT/HDCR enzymes mediating crotonylation/decrotonylation, must be involved in DSBs damage-induced Kcr of RPA1 and subsequent regulated DSB repair, which need to be revealed in future efforts.…”

Section: The Emerging Role Of Kcr In Dsb Repairmentioning

confidence: 99%

See 3 more Smart Citations

Lysine Crotonylation: An Emerging Player in DNA Damage Response

Zhao

Hao

et al. 2022

Biomolecules

View full text Add to dashboard Cite

The DNA damage response (DDR) system plays an important role in maintaining genome stability and preventing related diseases. The DDR network comprises many proteins and posttranslational modifications (PTMs) to proteins, which work in a coordinated manner to counteract various genotoxic stresses. Lysine crotonylation (Kcr) is a newly identified PTM occurring in both core histone and non-histone proteins in various organisms. This novel PTM is classified as a reversible acylation modification, which is regulated by a variety of acylases and deacylases and the intracellular crotonyl-CoA substrate concentration. Recent studies suggest that Kcr links cellular metabolism with gene regulation and is involved in numerous cellular processes. In this review, we summarize the regulatory mechanisms of Kcr and its functions in DDR, including its involvement in double-strand break (DSB)-induced transcriptional repression, DSB repair, and the DNA replication stress response.

show abstract

Section: Histone Kcr Is a New Determinant Of Double-strand Break (Dsb...mentioning

confidence: 99%

Section: Histone Kcr Is a New Determinant Of Double-strand Break (Dsb...mentioning

confidence: 99%

Section: Histone Kcr Is a New Determinant Of Double-strand Break (Dsb...mentioning

confidence: 99%

Section: The Emerging Role Of Kcr In Dsb Repairmentioning

confidence: 99%

See 2 more Smart Citations

Lysine Crotonylation: An Emerging Player in DNA Damage Response

Zhao

Hao

et al. 2022

Biomolecules

View full text Add to dashboard Cite

show abstract

“…From then on, there was a growing interest in Kcr because it has emerged as a powerful novel epigenetic marker. Histone Kcr has been associated with DNA damage and repair, transcriptional silencing and repair, carcinogenesis, kidney injury, inflammation, the building of some sperm super-enhancers, endoderm differentiation ( 19 , 20 ), and depressive behaviors. In addition to histone lysine residues, there are global profiles of the Kcr proteome in humans, animals, microorganisms, and plants ( 21 , 22 ).…”

Section: Introductionmentioning

confidence: 99%

Global crotonylatome and GWAS revealed a TaSRT1 - TaPGK model regulating wheat cold tolerance through mediating pyruvate

et al. 2023

View full text Add to dashboard Cite

Here, we reported the complete profiling of the crotonylation proteome in common wheat. Through a combination of crotonylation and multi-omics analysis, we identified a TaPGK associated with wheat cold stress. Then, we confirmed the positive role of TaPGK-modulating wheat cold tolerance. Meanwhile, we found that cold stress induced lysine crotonylation of TaPGK. Moreover, we screened a lysine decrotonylase TaSRT1 interacting with TaPGK and found that TaSRT1 negatively regulated wheat cold tolerance. We subsequently demonstrated TaSRT1 inhibiting the accumulation of TaPGK protein, and this inhibition was possibly resulted from decrotonylation of TaPGK by TaSRT1. Transcriptome sequencing indicated that overexpression of TaPGK activated glycolytic key genes and thereby increased pyruvate content. Moreover, we found that exogenous application of pyruvate sharply enhanced wheat cold tolerance. These findings suggest that the TaSRT1-TaPGK model regulating wheat cold tolerance is possibly through mediating pyruvate. This study provided two valuable cold tolerance genes and dissected diverse mechanism of glycolytic pathway involving in wheat cold stress.

show abstract

Protein lysine four‐carbon acylations in health and disease

Fang

2023

Journal Cellular Physiology

View full text Add to dashboard Cite

Lysine acylation, a type of posttranslational protein modification sensitive to cellular metabolic states, influences the functions of target proteins involved in diverse cellular processes. Particularly, lysine butyrylation, crotonylation, β‐hydroxybutyrylation, and 2‐hydroxyisobutyrylation, four types of four‐carbon acylations, are modulated by intracellular concentrations of their respective acyl‐CoAs and sensitive to alterations of nutrient metabolism induced by cellular and/or environmental signals. In this review, we discussed the metabolic pathways producing these four‐carbon acyl‐CoAs, the regulation of lysine acylation and deacylation, and the functions of individual lysine acylation.

show abstract

CDYL1-dependent decrease in lysine crotonylation at DNA double-strand break sites functionally uncouples transcriptional silencing and repair

Cited by 17 publications

References 82 publications

Lysine Crotonylation: An Emerging Player in DNA Damage Response

Lysine Crotonylation: An Emerging Player in DNA Damage Response

Global crotonylatome and GWAS revealed a TaSRT1 - TaPGK model regulating wheat cold tolerance through mediating pyruvate

Protein lysine four‐carbon acylations in health and disease

Contact Info

Product

Resources

About