Recognition of Histone Crotonylation by Taf14 Links Metabolic State to Gene Expression

Gowans, Graeme J.; Bridgers, Joseph B.; Zhang, Jibo; Dronamraju, Raghuvar; Burnetti, Anthony; King, D. A.; Thiengmany, Aline; Shinsky, Stephen A.; Bhanu, Natarajan V.; Garcia, Benjamin A.; Buchler, Nicolas E.; Strahl, Brian D.; Morrison, Ashby J.

doi:10.1016/j.molcel.2019.09.029

Cited by 90 publications

(95 citation statements)

References 55 publications

(101 reference statements)

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“…The level of histone acylation usually depends on the availability of its cognate metabolic precursor and is regulated in a dynamic manner. For example, a recent study showed that histone crotonylation and acetylation oscillate inversely during the yeast metabolic cycle, and elevated histone crotonylation upon nutrient limitation is coincident with periodical upregulation of fatty acid β-oxidation pathway and suppression of pro-growth genes; remarkably, a normal crotonyl-CoA metabolism as well as Kcr readout by the YEATS domain of Taf14 are necessary to maintain transcription oscillations during this process ( 50 ). Here, we confirmed inducible upregulation of histone benzoylation in cell and animal in response to NaBz treatment, and characterized DPF and YEATS family proteins, especially YEATS2, as histone benzoylation readers.…”

Section: Discussionmentioning

confidence: 99%

Histone benzoylation serves as an epigenetic mark for DPF and YEATS family proteins

Ren

Zhou

Xue

et al. 2020

Nucleic Acids Research

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Histone modifications and their functional readout serve as an important mechanism for gene regulation. Lysine benzoylation (Kbz) on histones is a recently identified acylation mark associated with active transcription. However, it remains to be explored whether putative readers exist to recognize this epigenetic mark. Here, our systematic binding studies demonstrated that the DPF and YEATS, but not the Bromodomain family members, are readers for histone Kbz. Co-crystal structural analyses revealed a ‘hydrophobic encapsulation’ and a ‘tip-sensor’ mechanism for Kbz readout by DPF and YEATS, respectively. Moreover, the DPF and YEATS family members display subtle yet unique features to create somewhat flexible engagements of different acylation marks. For instance, YEATS2 but not the other YEATS proteins exhibits best preference for Kbz than lysine acetylation and crotonylation due to its wider ‘tip-sensor’ pocket. The levels of histone benzoylation in cultured cells or in mice are upregulated upon sodium benzoate treatment, highlighting its dynamic regulation. In summary, our work identifies the first readers for histone Kbz and reveals the molecular basis underlying Kbz recognition, thus paving the way for further functional dissections of histone benzoylation.

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Section: Discussionmentioning

confidence: 99%

Histone benzoylation serves as an epigenetic mark for DPF and YEATS family proteins

Ren

Zhou

Xue

et al. 2020

Nucleic Acids Research

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“…However, the putative interplay between metabolism and histone acetylation remains to be explored during sporulation. It is particularly interesting to note that metabolic signaling and transcription has recently been linked through histone crotonylation and Taf14, which represses pro-growth genes upon activation of fatty acid ß-oxidation genes [ 71 ].…”

Section: Discussionmentioning

confidence: 99%

Systematic genetic and proteomic screens during gametogenesis identify H2BK34 methylation as an evolutionary conserved meiotic mark

Crespo

Luense

Arlotto

et al. 2020

Epigenetics & Chromatin

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Background Gametes are highly differentiated cells specialized to carry and protect the parental genetic information. During male germ cell maturation, histone proteins undergo distinct changes that result in a highly compacted chromatin organization. Technical difficulties exclude comprehensive analysis of precise histone mutations during mammalian spermatogenesis. The model organism Saccharomyces cerevisiae possesses a differentiation pathway termed sporulation which exhibits striking similarities to mammalian spermatogenesis. This study took advantage of this yeast pathway to first perform systematic mutational and proteomics screens on histones, revealing amino acid residues which are essential for the formation of spores. Methods A systematic mutational screen has been performed on the histones H2A and H2B, generating ~ 250 mutants using two genetic backgrounds and assessing their ability to form spores. In addition, histones were purified at key stages of sporulation and post-translational modifications analyzed by mass spectrometry. Results The mutation of 75 H2A H2B residues affected sporulation, many of which were localized to the nucleosome lateral surface. The use of different genetic backgrounds confirmed the importance of many of the residues, as 48% of yeast histone mutants exhibited impaired formation of spores in both genetic backgrounds. Extensive proteomic analysis identified 67 unique post-translational modifications during sporulation, 27 of which were previously unreported in yeast. Furthermore, 33 modifications are located on residues that were found to be essential for efficient sporulation in our genetic mutation screens. The quantitative analysis of these modifications revealed a massive deacetylation of all core histones during the pre-meiotic phase and a close interplay between H4 acetylation and methylation during yeast sporulation. Methylation of H2BK37 was also identified as a new histone marker of meiosis and the mouse paralog, H2BK34, was also enriched for methylation during meiosis in the testes, establishing conservation during mammalian spermatogenesis. Conclusion Our results demonstrate that a combination of genetic and proteomic approaches applied to yeast sporulation can reveal new aspects of chromatin signaling pathways during mammalian spermatogenesis.

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“…However, two recent studies have revealed roles of histone Kcr in transcriptional repression. Notably, in response to an increase of histone Kcr, down-regulated genes displayed a simultaneous decrease of histone Kac in the metabolic cycle of yeast and NEAT-knockdown cells [32, 33]. Therefore, the balance between the opposite changes of histone Kcr and Kac, accompanied by the complex crosstalk among histone PTMs, makes it difficult and ambiguous to determine whether histone Kcr directly represses transcription.…”

Section: Discussionmentioning

confidence: 99%

Histone lysine crotonylation regulates cell-fate determination of neural stem/progenitor cells by activating bivalent promoters

Liu

Dai

et al. 2020

Preprint

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Histone lysine crotonylation (Kcr), an evolutionarily conserved and widely expressed non-acetyl short-chain lysine acylation, plays important roles in transcriptional regulation and disease development. However, its genome-wide distribution, correlation with gene expression, and dynamic changes during developmental processes are largely unknown. In this study, we find that histone Kcr is mainly distributed in active promoters, has a ge-nome-wide positive correlation with transcriptional activity, and regulates transcription of genes participating in metabolism and proliferation. Moreover, elevated histone Kcr activates bivalent promoters to stimulate gene expression in neural stem/progenitor cells (NSPCs), through increasing chromatin openness and recruitment of RNA polymerase II (Pol II). Functionally, these activated genes remodel transcriptome and promote neuronal differentiation.Author summaryOverall, histone Kcr marks active promoters with high gene expression and modifies the local chromatin environment to allow gene activation, which influences neuronal cell fate. It may represent a unique active histone mark involved in neural developmental regulation.

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Recognition of Histone Crotonylation by Taf14 Links Metabolic State to Gene Expression

Cited by 90 publications

References 55 publications

Histone benzoylation serves as an epigenetic mark for DPF and YEATS family proteins

Histone benzoylation serves as an epigenetic mark for DPF and YEATS family proteins

Systematic genetic and proteomic screens during gametogenesis identify H2BK34 methylation as an evolutionary conserved meiotic mark

Histone lysine crotonylation regulates cell-fate determination of neural stem/progenitor cells by activating bivalent promoters

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