Why do eukaryotic cells employ ATP-consuming reaction cycles to regulate transcription?

24 March 2023

Hinrich Boeger
Department of Molecular, Cell and Developmental Biology
UC Santa Cruz

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Abstract

Transcriptionally induced promoters of eukaryotic genes are thought to randomly transition between alternative nucleosome configurations, including the nucleosome-free and fully nucleosomal promoter, the prevailing configuration in repressing conditions. While the purpose of nucleosome removal for transcription is evident – the nucleosome is a general repressor of transcription – the goal of nucleosome reformation in activating conditions is not. Both formation and removal of nucleosomes are catalyzed by ATP-dependent chromatin remodelers. In steady state, the net result appears to be no other than ATP hydrolysis. Do ATP-fueled promoter nucleosome dynamics serve a purpose, or do they represent a futile cycle, the expenditure of free energy to no effect? I shall argue that the answer is 'no' – that the recruitment of ATP-dependent chromatin remodelers to promoters by transcriptional activators reconciles the dual requirements for regulatory speed and specificity and that bacteria solve the same problem in a fundamentally different way.

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