Identification of histone code for DNA replication-independent histone turnover in Schizosaccharomyces pombe = 분열효모에서 DNA 복제 비의존적 염색질 교환에 관여하는 히스톤 코드에 관한 연구

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Most protein-coding genes are transcribed by RNA polymerase II (Pol II) in eukaryotic cells. To overcome obstacles exerted by chromatin, Pol II constantly removes histones and proceeds with transcription. Cumulative evidence indicates reassembly of evicted histones by chromatin factors, a mechanism known as histone turnover, to maintain proper chromatin structure during transcription. In this study, to understand the molecular details about histone turnover in Schizosaccharomyces pombe (S. pombe), a replication-independent histone turnover assay was established through incorporation of newly synthesized histones into chromatin. Significant histone turnover was observed in nucleosome-free regions (NFRs) and showed high correlations with transcription rate. The patterns of histone turnover were categorized into three clusters and some genes of cluster3 appeared to be subjects of DNA replication- and transcription-independent histone turnover. Interestingly, histone marks such as H3K56 acetylation (H3K56Ac) and H4K20 monomethylation (H4K20me1) were localized at NFRs and these marks were highly correlated with expression levels. Genome-wide profiles of H3K56Ac were similar between S. pombe and Saccharomyces cerevisiae. Surprisingly, the genome-wide occupancy of H4K20me1 overlapped with H3K56Ac occupancy. In set2 and alp13 mutants, aberrant antisense transcripts were produced at coding regions, possibly due to histone turnover. In genome-wide ChIP-seq, levels of H3K56Ac and H4K20me1 in set2 and alp13 deletion cells were found to be increased compared to wild-type, indicating that H4K20me1 may serve as a histone turnover mark in S. pombe, in addition to H3K56Ac. A correlation between histone turnover, H3K56Ac and H4K20me1 was assessed in asynchronized cells. H3K56Ac showed a positive correlation with histone turnover, in both synchronized and asynchronized cells, whereas H4K20me1 showed strong correlations with histone turnover when the experimental conditions were similar. These findings indicate that H3K56Ac stands for histone turnover in both replication-dependent and -independent manners while H4K20me1 only serves as a mark in a transcription-dependent manner.
Lee, Daeyoupresearcher이대엽researcher
한국과학기술원 :생명과학과,
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학위논문(박사) - 한국과학기술원 : 생명과학과, 2016.8 ,[vi, 100 p. :]


chromatin; histone turnover; histone turnover mark; H3K56 acetylation; H4K20 monomethylaiton; 염색질; 염색질 교환; 염색질 교환 표시자

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