Promoter regulation by distinct mechanisms of functional interplay between lysine acetylase Rtt109 and histone chaperone Asf1

Department of Biochemistry, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB, Canada T6G 2H7.
Proceedings of the National Academy of Sciences (Impact Factor: 9.67). 11/2011; 108(49):19599-604. DOI: 10.1073/pnas.1111501108
Source: PubMed


The promoter activity of yeast genes can depend on lysine 56 (K56) acetylation of histone H3. This modification of H3 is performed by lysine acetylase Rtt109 acting in concert with histone chaperone Asf1. We have examined the contributions of Rtt109, Asf1, and H3 K56 acetylation to nutrient regulation of a well-studied metabolic gene, ARG1. As expected, Rtt109, Asf1, and H3 K56 acetylation are required for maximal transcription of ARG1 under inducing conditions. However, Rtt109 and Asf1 also inhibit ARG1 under repressing conditions. This inhibition requires Asf1 binding to H3-H4 and Rtt109 KAT activity, but not tail acetylation of H3-H4 or K56 acetylation of H3. These observations suggest the existence of a unique mechanism of transcriptional regulation by Rtt109. Indeed, chromatin immunoprecipitation and genetic interaction studies support a model in which promoter-targeted Rtt109 represses ARG1 by silencing a pathway of transcriptional activation that depends on ASF1. Collectively, our results show that ARG1 transcription intensity at its induced and repressed set points is controlled by different mechanisms of functional interplay between Rtt109 and Asf1.

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Available from: Kathy Lin, May 20, 2014
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    • "This study brings forth a functional overlap between transcription, replication, and chromosome architecture mediated by Asf1. Asf1 binding to chromatin has been envisaged as non-specific [24], [28]. Its binding to only a fraction of the pol II-transcribed genes suggests that its reported roles in genome-wide histone exchange and transcription regulation may be indirect or redundant with other chaperones. "
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