Department of Proteomics, The Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3B, 2200, Copenhagen, Denmark.
Nat Commun. 2024 Jun 11;15(1):4962. doi: 10.1038/s41467-024-49370-2.
In all eukaryotes, acetylation of histone lysine residues correlates with transcription activation. Whether histone acetylation is a cause or consequence of transcription is debated. One model suggests that transcription promotes the recruitment and/or activation of acetyltransferases, and histone acetylation occurs as a consequence of ongoing transcription. However, the extent to which transcription shapes the global protein acetylation landscapes is not known. Here, we show that global protein acetylation remains virtually unaltered after acute transcription inhibition. Transcription inhibition ablates the co-transcriptionally occurring ubiquitylation of H2BK120 but does not reduce histone acetylation. The combined inhibition of transcription and CBP/p300 further demonstrates that acetyltransferases remain active and continue to acetylate histones independently of transcription. Together, these results show that histone acetylation is not a mere consequence of transcription; acetyltransferase recruitment and activation are uncoupled from the act of transcription, and histone and non-histone protein acetylation are sustained in the absence of ongoing transcription.
在所有真核生物中，组蛋白赖氨酸残基的乙酰化与转录激活相关。组蛋白乙酰化是转录的原因还是结果仍存在争议。一种模型表明，转录促进乙酰转移酶的募集和/或激活，并且组蛋白乙酰化是转录过程中的一个结果。然而，转录在多大程度上塑造了全局蛋白质乙酰化景观尚不清楚。在这里，我们表明急性转录抑制后，全局蛋白质乙酰化几乎没有变化。转录抑制消除了 H2BK120 的共转录发生泛素化，但不会降低组蛋白乙酰化。转录和 CBP/p300 的联合抑制进一步表明，乙酰转移酶仍然保持活性，并独立于转录继续乙酰化组蛋白。综上所述，这些结果表明组蛋白乙酰化不仅仅是转录的结果；乙酰转移酶的募集和激活与转录过程脱钩，并且在没有持续转录的情况下，组蛋白和非组蛋白蛋白质的乙酰化得以维持。
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