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H3.3-H4 tetramer splitting events feature cell-type specific enhancers.
Chang Huang1, Zhuqiang Zhang, Mo Xu
1College of Biological Sciences, China Agricultural University, Beijing, China.
Plos Genetics
|June 12, 2013
Summary
Histone variant H3.3 nucleosomes split during cell division, with splitting events marking active genes and enhancers. This splitting, particularly at enhancers, may actively regulate cell-type specific transcription.
Area of Science:
- Epigenetics
- Molecular Biology
- Genomics
Background:
- Canonical histone tetramers (H3.1-H4)2 show limited splitting, forming hybrid tetramers.
- Histone variant H3.3 tetramers (H3.3-H4)2 exhibit significant splitting (~10%) each cell cycle.
Purpose of the Study:
- To map genome-wide H3.3 nucleosome occupancy, turnover, and splitting events.
- To investigate the relationship between H3.3 dynamics and gene expression.
- To explore the role of H3.3 nucleosome splitting at enhancers.
Main Methods:
- Genome-wide mapping of H3.3 nucleosome occupancy.
- Analysis of H3.3 nucleosome turnover rates.
- Identification and analysis of H3.3 nucleosome splitting events.
Main Results:
- H3.3 turnover at transcription start sites (TSS) shows a bimodal distribution, correlating with gene activity (high turnover in active genes, low in inactive).
- H3.3 nucleosome splitting events are enriched at active genes, serving as a better marker of transcription than occupancy.
- H3.3 nucleosome splitting events are moderately correlated with turnover but not a direct consequence, and are highly enriched at cell-type specific enhancers.
Conclusions:
- H3.3 nucleosome splitting is a distinct process from turnover and is strongly associated with active transcription.
- H3.3 nucleosomes at enhancers exhibit high splitting rates in a cell-type specific manner.
- H3.3 nucleosome splitting at enhancers may be an active mechanism regulating cell-type specific gene expression.
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