Histones and non-histone proteins are acetylated without ongoing transcription

The acetylation of multiple histone lysine residues in all eukaryotes is known to be associated with transcription activation. However, the causal relationship between histone acetylation and transcription remains a topic of debate. One hypothesis proposes that transcription plays a role in recruiting and activating acetyltransferases, resulting in histone acetylation as a consequence of ongoing transcription. Nevertheless, the extent to which transcription influences the overall acetylation patterns across the genome remains uncertain. This study aims to shed light on this matter by investigating the impact of acute transcription inhibition on global protein acetylation. Surprisingly, the findings demonstrate that global protein acetylation levels remain largely unaffected even after inhibiting transcription. While transcription inhibition leads to the cessation of co-transcriptional ubiquitylation of H2BK120, histone acetylation persists. This suggests that histone acetylation is not solely dependent on transcriptional activity. Moreover, the study delves deeper into the relationship between transcription and acetyltransferase activity. By jointly inhibiting transcription and CBP/p300 it was observed that acetyltransferases remained active and continued to acetylate histones independently of inhibited transcription. Collectively, these results challenge the idea that histone acetylation is merely a consequence of transcription. Instead, they indicate that acetyltransferase recruitment and activation are not directly coupled to the process of transcription. Furthermore, the acetylation of both histone and non-histone proteins persists even in the absence of ongoing transcription. This highlights the complexity of histone acetylation regulation and suggests that it may not be solely dictated by the presence or absence of transcriptional activity.