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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 nucleosomes with higher turnover index tend to associate with higher splitting index.(A) The distribution of splitting index for H3.3 nucleosomes within each specified turnover index range. (B) The distribution of splitting index for H3.3 nucleosomes within the highest turnover index ranges.
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pgen-1003558-g003: H3.3 nucleosomes with higher turnover index tend to associate with higher splitting index.(A) The distribution of splitting index for H3.3 nucleosomes within each specified turnover index range. (B) The distribution of splitting index for H3.3 nucleosomes within the highest turnover index ranges.

Mentions: Secondly, at regions with the highest turnover rate, it is a concern that our approach may fail to capture the split nucleosomes. To clarify this concern, we categorized all H3.3 nucleosomes according to their turnover index (T48) range and compared their splitting index. H3.3 nucleosomes with higher turnover index clearly associated with higher splitting index (Figure 3A). To obtain an amplified view for H3.3 nucleosomes with the highest turnover rate, we further categorized these nucleosomes according to their turnover index (T48) range, and observed a similar trend, with the exception of the last group (T48 range 0.99–1.0). But there were only 13 H3.3 nucleosomes defined in this group, and the results for this group may not be statistically meaningful. Taken together, H3.3 nucleosomes with the highest turnover index (T48) generally displayed the highest splitting index, suggesting that our approach could capture the splitting events at regions with the highest turnover.


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 nucleosomes with higher turnover index tend to associate with higher splitting index.(A) The distribution of splitting index for H3.3 nucleosomes within each specified turnover index range. (B) The distribution of splitting index for H3.3 nucleosomes within the highest turnover index ranges.
© Copyright Policy
Related In: Results  -  Collection

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

pgen-1003558-g003: H3.3 nucleosomes with higher turnover index tend to associate with higher splitting index.(A) The distribution of splitting index for H3.3 nucleosomes within each specified turnover index range. (B) The distribution of splitting index for H3.3 nucleosomes within the highest turnover index ranges.
Mentions: Secondly, at regions with the highest turnover rate, it is a concern that our approach may fail to capture the split nucleosomes. To clarify this concern, we categorized all H3.3 nucleosomes according to their turnover index (T48) range and compared their splitting index. H3.3 nucleosomes with higher turnover index clearly associated with higher splitting index (Figure 3A). To obtain an amplified view for H3.3 nucleosomes with the highest turnover rate, we further categorized these nucleosomes according to their turnover index (T48) range, and observed a similar trend, with the exception of the last group (T48 range 0.99–1.0). But there were only 13 H3.3 nucleosomes defined in this group, and the results for this group may not be statistically meaningful. Taken together, H3.3 nucleosomes with the highest turnover index (T48) generally displayed the highest splitting index, suggesting that our approach could capture the splitting events at regions with the highest turnover.

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