Intracellular Crotonyl-CoA Stimulates Transcription through p300-Catalyzed Histone Crotonylation

Sabari, Benjamin R.; Tang, Zhanyun; Huang, He; Yong-Gonzalez, Vladimir; Molina, Henrik; Kong, Ha Eun; Dai, Lunzhi; Shimada, Miho; Cross, Justin R.; Zhao, Yingming; Roeder, Robert G.; Allis, C. David

doi:10.1016/j.molcel.2018.01.013

Cited by 75 publications

(117 citation statements)

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“…In addition, histone crotonylation was enriched on sex chromosomes and specifically marked X‐linked genes that escaped sex chromosome inactivation in male germinal cells immediately following meiosis. A recent study reported p300‐mediated histone crotonylation stimulates gene transcription to a greater degree than histone acetylation . With a cell‐based model of transcriptional activation, they also suggested different level of cellular crotonyl‐CoA concentration led the changes in histone crotonylation levels flanking the regulatory elements of activated genes and was correlated with gene expression.…”

Section: Functional Roles Of Lysine Crotonylationmentioning

confidence: 96%

“…Sabari et al 25 first reported that p300 has both HAT and HCT activities. In the cell-free assays, they demonstrated that p300-catalysed histone crotonylation directly stimulated transcription to a greater degree than p300-catalysed histone acetylation.…”

Section: Writer S Of Lys Ine Crotonyl Ati Onmentioning

confidence: 99%

“…In vivo Descriptive study Meiotic and postmeiotic male germ cells and tissues 2011 11 Cell culture Interventional study 293T cells 2017 26 Cell culture Interventional study HeLa cells 2017 31 Ex vivo and cell culture Interventional study Cell-free system and LPS induced inflammatory response in the macrophage cell line RAW 264.7 2018 37 Regulation of acute kidney injury…”

Section: Regulation Of Gene Transcriptionmentioning

confidence: 99%

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Functions and mechanisms of lysine crotonylation

Wan

Chu

et al. 2019

J Cellular Molecular Medi

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Lysine crotonylation is a newly discovered post‐translational modification, which is structurally and functionally different from the widely studied lysine acetylation. Recent advances in the identification and quantification of lysine crotonylation by mass spectrometry have revealed that non‐histone proteins are frequently crotonylated, implicating it in many biological processes through the regulation of chromatin remodelling, metabolism, cell cycle and cellular organization. In this review, we summarize the writers, erasers and readers of lysine crotonylation, and their physiological functions, including gene transcription, acute kidney injury, spermatogenesis, depression, telomere maintenance, HIV latency and cancer process. These findings not only point to the new functions for lysine crotonylation, but also highlight the mechanisms by which crotonylation regulates various cellular processes.

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Section: Functional Roles Of Lysine Crotonylationmentioning

confidence: 96%

Section: Writer S Of Lys Ine Crotonyl Ati Onmentioning

confidence: 99%

Section: Regulation Of Gene Transcriptionmentioning

confidence: 99%

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Functions and mechanisms of lysine crotonylation

Wan

Chu

et al. 2019

J Cellular Molecular Medi

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“…Tan et al found that histone lysine crotonylation, as a strong transcriptional activator, marks the enhancers and transcription start sites of active genes in the human somatic cell genome. The study indicates that the transcriptional coactivator p300 which has an intrinsic histone crotonyltransferase (HCT) activity, can catalyze histone crotonylation, and levels of histone crotonylation are modulated by the cellular concentration of crotonyl-CoA (Sabari et al, 2015).…”

Section: Crotonylationmentioning

confidence: 99%

Elevated lysine crotonylation and succinylation in the brains of BTBR mice

Wang

Chang

Yang

et al. 2019

Intl J of Devlp Neuroscience

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The BTBR T + Itpr3tf/J (BTBR) mouse has developmental disorders in the central nervous system and many aberrant neuroanatomical structures. However, identification of the pathological mechanisms underlying these abnormal neuroanatomical structures in the brains of BTBR mice is still lacking. Posttranslational modifications (PTMs) are known to be involved in the regulation of diverse cellular processes, and evidence shows that some types of PTMs are associated with the development of the central nervous system. In this study, we detected four novel PTMs in the cerebral cortex of BTBR mice as compared to C57BL/6 J (B6) mice using western blotting. Results revealed that lysine crotonylation and succinylation were elevated in the cerebral cortex of BTBR mice compared to levels in B6 mice. We speculate that elevated profiles of lysine crotonylation and succinylation may be involved in mechanisms related to neuroanatomical abnormalities in cerebral cortex of BTBR mice.

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“…In the case of enzymatic acetylation, lysine acetyltransferases (KATs, also referred to as histone acetyltransferases or HATs) transfer an acetyl group from acetyl-CoA to a lysine residue (Roth et al 2001). Although originally reported to acetylate histones only, KATs also acetylate non-histone proteins in different compartments of the cell and members of the p300/CREB family of KATs have been shown to catalyze propionylation, butyrylation, crotonylation and succinylation as well (Chen et al 2007;Cheng et al 2009;Tan et al 2014;Hirschey and Zhao 2015;Sabari et al 2015). In mitochondria, where acetylation is highly abundant (Kim et al 2006), GCN5L1 was reported as a mitochondrial acetyltransferase (Scott et al 2012).…”

Section: Lysine Acylationmentioning

confidence: 99%

Sirtuin activation as a therapeutic approach against inborn errors of metabolism

Bleeker

Houtkooper

2016

J of Inher Metab Disea

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Protein acylation has emerged as a large family of post translational modifications in which an acyl group can alter the function of a wide variety of proteins, especially in response to metabolic stress. The acylation state is regulated through reversible acylation/deacylation. Acylation occurs enzymatically or non-enzymatically, and responds to acyl-CoA levels. Deacylation on the other hand is controlled through the NAD+-dependent sirtuin proteins. In several inborn errors of metabolism (IEMs), accumulation of acyl-CoAs, due to defects in amino acid and fatty acid metabolic pathways, can lead to hyperacylation of proteins. This can have a direct effect on protein function and might play a role in pathophysiology. In this review we describe several mouse and cell models for IEM that display high levels of lysine acylation. Furthermore, we discuss how sirtuins serve as a promising therapeutic target to restore acylation state and could treat IEMs. In this context we examine several pharmacological sirtuin activators, such as resveratrol, NAD+ precursors and PARP and CD38 inhibitors.

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Intracellular Crotonyl-CoA Stimulates Transcription through p300-Catalyzed Histone Crotonylation

Cited by 75 publications

References 0 publications

Functions and mechanisms of lysine crotonylation

Functions and mechanisms of lysine crotonylation

Elevated lysine crotonylation and succinylation in the brains of BTBR mice

Sirtuin activation as a therapeutic approach against inborn errors of metabolism

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