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Histone variant Htz1 promotes histone H3 acetylation to enhance nucleotide excision repair in Htz1 nucleosomes.

ABSTRACT: Nucleotide excision repair (NER) is critical for maintaining genome integrity. How chromatin dynamics are regulated to facilitate this process in chromatin is still under exploration. We show here that a histone H2A variant, Htz1 (H2A.Z), in nucleosomes has a positive function in promoting efficient NER in yeast. Htz1 inherently enhances the occupancy of the histone acetyltransferase Gcn5 on chromatin to promote histone H3 acetylation after UV irradiation. Consequently, this results in an increased binding of a NER protein, Rad14, to damaged DNA. Cells without Htz1 show increased UV sensitivity and defective removal of UV-induced DNA damage in the Htz1-bearing nucleosomes at the repressed MFA2 promoter, but not in the HMRa locus where Htz1 is normally absent. Thus, the effect of Htz1 on NER is specifically relevant to its presence in chromatin within a damaged region. The chromatin accessibility to micrococcal nuclease in the MFA2 promoter is unaffected by HTZ1 deletion. Acetylation on previously identified lysines of Htz1 plays little role in NER or cell survival after UV. In summary, we have identified a novel aspect of chromatin that regulates efficient NER, and we provide a model for how Htz1 influences NER in Htz1 nucleosomes.

SUBMITTER: Yu Y

PROVIDER: S-EPMC3799447 | biostudies-literature | 2013 Oct

REPOSITORIES: biostudies-literature

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Histone variant Htz1 promotes histone H3 acetylation to enhance nucleotide excision repair in Htz1 nucleosomes.

Yu Yachuan Y Deng Yanbo Y Reed Simon H SH Millar Catherine B CB Waters Raymond R

Nucleic acids research 20130807 19

Nucleotide excision repair (NER) is critical for maintaining genome integrity. How chromatin dynamics are regulated to facilitate this process in chromatin is still under exploration. We show here that a histone H2A variant, Htz1 (H2A.Z), in nucleosomes has a positive function in promoting efficient NER in yeast. Htz1 inherently enhances the occupancy of the histone acetyltransferase Gcn5 on chromatin to promote histone H3 acetylation after UV irradiation. Consequently, this results in an increa ...[more]

PMID: 23925126

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Project description:Candida albicans is an opportunistic human pathogen that colonizes the gastrointestinal and genitourinary tracts of healthy individuals. C. albicans yeast cells can switch to filamentous forms. On biotic and abiotic surfaces, the planktonic free-floating yeast cells often form biofilms, a multi-drug-resistant three-dimensional community of yeast and filamentous cells. While alterations in gene expression patterns during planktonic to biofilm growth transitions in C. albicans have been studied, the underlying molecular mechanisms largely remain unexplored. Previously, we identified a histone H3 variant (H3VCTG), which acts as a negative regulator of biofilm growth in C. albicans. In the current study, we performed genome-wide profiling of H3VCTG nucleosomes in C. albicans planktonic cells and found them to be enriched at promoter regions. In planktonic cells, H3VCTG-enriched regions are mostly devoid of histone H3 post-translational modifications that allow active transcription, thus strengthening the role of H3VCTG as a negative regulator of biofilm formation. By combining genome-wide transcriptional alterations, nucleosome positioning (MNase-seq), and DNA accessibility (ATAC-seq) assays, we show a significant reduction in the total number of nucleosomes in biofilm cells as compared to planktonic cells indicating a more open chromatin state during biofilm growth. Finally, we propose that H3VCTG-nucleosome eviction at promoters of biofilm-relevant genes in biofilm-grown cells contributes to achieve the open chromatin state by facilitating easy promoter access of master regulators (activators and repressors) for modulation of gene expression observed during growth phase transitions. IMPORTANCE Candida albicans lives as a commensal in most healthy humans but can cause superficial skin infections to life-threatening systemic infections. C. albicans also forms biofilms on biotic and abiotic surfaces. Biofilm cells are difficult to treat and highly resistant to antifungals. A specific set of genes is differentially regulated in biofilm cells as compared to free-floating planktonic cells of C. albicans. In this study, we addressed how a variant histone H3VCTG, a previously identified negative regulator of biofilm formation, modulates gene expression changes. By providing compelling evidence, we show that biased eviction of H3VCTG nucleosomes at the promoters of biofilm-relevant genes facilitates the accessibility of both transcription activators and repressors to modulate gene expression. Our study is a comprehensive investigation of genome-wide nucleosome occupancy in both planktonic and biofilm states, which reveals transition to an open chromatin landscape during biofilm mode of growth in C. albicans, a medically relevant pathogen.

Dataset Information

Histone variant Htz1 promotes histone H3 acetylation to enhance nucleotide excision repair in Htz1 nucleosomes.

Publications

Histone variant Htz1 promotes histone H3 acetylation to enhance nucleotide excision repair in Htz1 nucleosomes.

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