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H3.3-H4 tetramer splitting events feature cell-type specific enhancers.

Huang C, Zhang Z, Xu M, Li Y, Li Z, Ma Y, Cai T, Zhu B - PLoS Genet. (2013)

Bottom Line: H3.3 nucleosome splitting events are enriched at active genes, which are in fact better markers for active transcription than H3.3 nucleosome occupancy itself.Surprisingly, H3.3 nucleosomes with high splitting index are remarkably enriched at enhancers in a cell-type specific manner.We propose that the H3.3 nucleosomes at enhancers may be split by an active mechanism to regulate cell-type specific transcription.

View Article: PubMed Central - PubMed

Affiliation: College of Biological Sciences, China Agricultural University, Beijing, China.

ABSTRACT
Previously, we reported that little canonical (H3.1-H4)(2) tetramers split to form "hybrid" tetramers consisted of old and new H3.1-H(4) dimers, but approximately 10% of (H3.3-H4)2 tetramers split during each cell cycle. In this report, we mapped the H3.3 nucleosome occupancy, the H3.3 nucleosome turnover rate and H3.3 nucleosome splitting events at the genome-wide level. Interestingly, H3.3 nucleosome turnover rate at the transcription starting sites (TSS) of genes with different expression levels display a bimodal distribution rather than a linear correlation towards the transcriptional activity, suggesting genes are either active with high H3.3 nucleosome turnover or inactive with low H3.3 nucleosome turnover. H3.3 nucleosome splitting events are enriched at active genes, which are in fact better markers for active transcription than H3.3 nucleosome occupancy itself. Although both H3.3 nucleosome turnover and splitting events are enriched at active genes, these events only display a moderate positive correlation, suggesting H3.3 nucleosome splitting events are not the mere consequence of H3.3 nucleosome turnover. Surprisingly, H3.3 nucleosomes with high splitting index are remarkably enriched at enhancers in a cell-type specific manner. We propose that the H3.3 nucleosomes at enhancers may be split by an active mechanism to regulate cell-type specific transcription.

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H3.3 nucleosome splitting events feature cell-type specific enhancers.(A) An example enhancer region enriched with split H3.3 nucleosomes. Profiles of single-round ChIPs, sequential ChIP, turnover index, splitting index are illustrated. Percentile ranking of turnover index and splitting index are shown in a grey scale. (B) Split H3.3 nucleosomes were specifically enriched at enhancers, whereas the non-split H3.3 nucleosomes were specifically depleted at enhancers. (C) Distribution of the H3.3 nucleosomes, split and non-split H3.3 nucleosomes, intergenic split H3.3 nucleosomes and high and low turnover H3.3 nucleosomes at the cell-type specific enhancers. (D) All H3.3 nucleosomes were sorted by their splitting index and grouped into 5000 nucleosome widows. These nucleosomes were then plotted against their overlap percentage with enhancers. The arbitrarily defined split and non-split nucleosomes with top or bottom 5% splitting index were boxed in red. (E) Similar to (D), but common enhancers were excluded. (F) The 10-kb genomic intervals sorted by their numbers of split nucleosomes were plotted against their overlap percentage with the cell-type specific enhancers. (G) Similar to (F), but common enhancers were excluded.
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pgen-1003558-g006: H3.3 nucleosome splitting events feature cell-type specific enhancers.(A) An example enhancer region enriched with split H3.3 nucleosomes. Profiles of single-round ChIPs, sequential ChIP, turnover index, splitting index are illustrated. Percentile ranking of turnover index and splitting index are shown in a grey scale. (B) Split H3.3 nucleosomes were specifically enriched at enhancers, whereas the non-split H3.3 nucleosomes were specifically depleted at enhancers. (C) Distribution of the H3.3 nucleosomes, split and non-split H3.3 nucleosomes, intergenic split H3.3 nucleosomes and high and low turnover H3.3 nucleosomes at the cell-type specific enhancers. (D) All H3.3 nucleosomes were sorted by their splitting index and grouped into 5000 nucleosome widows. These nucleosomes were then plotted against their overlap percentage with enhancers. The arbitrarily defined split and non-split nucleosomes with top or bottom 5% splitting index were boxed in red. (E) Similar to (D), but common enhancers were excluded. (F) The 10-kb genomic intervals sorted by their numbers of split nucleosomes were plotted against their overlap percentage with the cell-type specific enhancers. (G) Similar to (F), but common enhancers were excluded.

Mentions: The H3.3 nucleosomes were reported to display cell-type specific enrichment at intergenic regions bound by multiple transcription factors, suggesting an enrichment of the H3.3 nucleosomes at the enhancers [9], which prompted us to interrogate the splitting events at the enhancers. Interestingly, it appears to be quite obvious that split H3.3 nucleosomes are enriched at a number of enhancers that we looked into (Figure 6A and Figure S3).


H3.3-H4 tetramer splitting events feature cell-type specific enhancers.

Huang C, Zhang Z, Xu M, Li Y, Li Z, Ma Y, Cai T, Zhu B - PLoS Genet. (2013)

H3.3 nucleosome splitting events feature cell-type specific enhancers.(A) An example enhancer region enriched with split H3.3 nucleosomes. Profiles of single-round ChIPs, sequential ChIP, turnover index, splitting index are illustrated. Percentile ranking of turnover index and splitting index are shown in a grey scale. (B) Split H3.3 nucleosomes were specifically enriched at enhancers, whereas the non-split H3.3 nucleosomes were specifically depleted at enhancers. (C) Distribution of the H3.3 nucleosomes, split and non-split H3.3 nucleosomes, intergenic split H3.3 nucleosomes and high and low turnover H3.3 nucleosomes at the cell-type specific enhancers. (D) All H3.3 nucleosomes were sorted by their splitting index and grouped into 5000 nucleosome widows. These nucleosomes were then plotted against their overlap percentage with enhancers. The arbitrarily defined split and non-split nucleosomes with top or bottom 5% splitting index were boxed in red. (E) Similar to (D), but common enhancers were excluded. (F) The 10-kb genomic intervals sorted by their numbers of split nucleosomes were plotted against their overlap percentage with the cell-type specific enhancers. (G) Similar to (F), but common enhancers were excluded.
© Copyright Policy
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC3675017&req=5

pgen-1003558-g006: H3.3 nucleosome splitting events feature cell-type specific enhancers.(A) An example enhancer region enriched with split H3.3 nucleosomes. Profiles of single-round ChIPs, sequential ChIP, turnover index, splitting index are illustrated. Percentile ranking of turnover index and splitting index are shown in a grey scale. (B) Split H3.3 nucleosomes were specifically enriched at enhancers, whereas the non-split H3.3 nucleosomes were specifically depleted at enhancers. (C) Distribution of the H3.3 nucleosomes, split and non-split H3.3 nucleosomes, intergenic split H3.3 nucleosomes and high and low turnover H3.3 nucleosomes at the cell-type specific enhancers. (D) All H3.3 nucleosomes were sorted by their splitting index and grouped into 5000 nucleosome widows. These nucleosomes were then plotted against their overlap percentage with enhancers. The arbitrarily defined split and non-split nucleosomes with top or bottom 5% splitting index were boxed in red. (E) Similar to (D), but common enhancers were excluded. (F) The 10-kb genomic intervals sorted by their numbers of split nucleosomes were plotted against their overlap percentage with the cell-type specific enhancers. (G) Similar to (F), but common enhancers were excluded.
Mentions: The H3.3 nucleosomes were reported to display cell-type specific enrichment at intergenic regions bound by multiple transcription factors, suggesting an enrichment of the H3.3 nucleosomes at the enhancers [9], which prompted us to interrogate the splitting events at the enhancers. Interestingly, it appears to be quite obvious that split H3.3 nucleosomes are enriched at a number of enhancers that we looked into (Figure 6A and Figure S3).

Bottom Line: H3.3 nucleosome splitting events are enriched at active genes, which are in fact better markers for active transcription than H3.3 nucleosome occupancy itself.Surprisingly, H3.3 nucleosomes with high splitting index are remarkably enriched at enhancers in a cell-type specific manner.We propose that the H3.3 nucleosomes at enhancers may be split by an active mechanism to regulate cell-type specific transcription.

View Article: PubMed Central - PubMed

Affiliation: College of Biological Sciences, China Agricultural University, Beijing, China.

ABSTRACT
Previously, we reported that little canonical (H3.1-H4)(2) tetramers split to form "hybrid" tetramers consisted of old and new H3.1-H(4) dimers, but approximately 10% of (H3.3-H4)2 tetramers split during each cell cycle. In this report, we mapped the H3.3 nucleosome occupancy, the H3.3 nucleosome turnover rate and H3.3 nucleosome splitting events at the genome-wide level. Interestingly, H3.3 nucleosome turnover rate at the transcription starting sites (TSS) of genes with different expression levels display a bimodal distribution rather than a linear correlation towards the transcriptional activity, suggesting genes are either active with high H3.3 nucleosome turnover or inactive with low H3.3 nucleosome turnover. H3.3 nucleosome splitting events are enriched at active genes, which are in fact better markers for active transcription than H3.3 nucleosome occupancy itself. Although both H3.3 nucleosome turnover and splitting events are enriched at active genes, these events only display a moderate positive correlation, suggesting H3.3 nucleosome splitting events are not the mere consequence of H3.3 nucleosome turnover. Surprisingly, H3.3 nucleosomes with high splitting index are remarkably enriched at enhancers in a cell-type specific manner. We propose that the H3.3 nucleosomes at enhancers may be split by an active mechanism to regulate cell-type specific transcription.

Show MeSH