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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    • "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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    ABSTRACT: Genome-wide participation and importance of the histone chaperone Asf1 (Anti-Silencing Function 1) in diverse DNA transactions like replication, repair, heterochromatic silencing and transcription are well documented. Yet its genome-wide targets have not been reported. Using ChIP-seq method, we found that yeast Asf1 associates with 590 unique targets including centromeres, telomeres and condensin-binding sites. It is found selectively on highly transcribed regions, which include replication fork pause sites. Asf1 preferentially associates with the genes transcribed by RNA polymerase (pol) III where its presence affects RNA production and replication-independent histone exchange. On pol II-transcribed genes, a negative correlation is found between Asf1 and nucleosome occupancy. It is not enriched on most of the reported sites of histone exchange or on the genes, which are misregulated in the asf1Δ cells. Interestingly, chromosome-wide distributions of Asf1 and one of the condensin subunits, Brn1 show a nearly identical pattern. Moreover, Brn1 shows reduced occupancy at various condensin-binding sites in asf1Δ cells. These results along with high association of Asf1 with heterochromatic centromeres and telomeres ascribe novel roles to Asf1 in condensin loading and chromatin dynamics.
    PLoS ONE 09/2014; 9(9):e108652. DOI:10.1371/journal.pone.0108652 · 3.23 Impact Factor
  • New Developments in Chromatin Research, 1 edited by Neil M. Simpson, Valerie J. Stewart, 08/2012: chapter 2: pages 29-58; Nova Science Publishers.
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    ABSTRACT: ANTI-SILENCING FUNCTION 1 (ASF1) is an evolutionarily conserved histone chaperone involved in diverse chromatin-based processes in eukaryotes. Yet, its role in transcription and the underlying molecular mechanisms remain largely elusive, particularly in plants. Here, we show that the Arabidopsis thaliana ASF1 homologous genes, AtASF1A and AtASF1B, are involved in gene transcription activation in response to heat stress. The Atasf1ab mutant displays defective basal as well as acquired thermotolerance phenotypes. Heat-induced expression of several key genes, including the HEAT SHOCK PROTEIN (HSP) genes Hsp101, Hsp70, Hsa32, Hsp17.6A and Hsp17.6B-CI, and the HEAT SHOCK FACTOR (HSF) gene HsfA2 but not HsfB1 is drastically impaired in Atasf1ab as compared to that in wild type. We found that AtASF1A/B proteins are recruited onto chromatin and their enrichment is correlated with nucleosome removal and RNA polymerase II accumulation at the promoter and coding regions of HsfA2 and Hsa32 but not HsfB1. Moreover, AtASF1A/B facilitate H3K56 acetylation (H3K56ac), which is associated with HsfA2 and Hsa32 activation. Taken together, our study unravels an important function of AtASF1A/B in plant heat stress response and suggests that AtASF1A/B participate in transcription activation of some but not all HSF and HSP genes via nucleosome removal and H3K56ac stimulation.
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