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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 are better markers for active transcription than H3.3 nucleosome occupancy.(A) Split H3.3 nucleosomes were enriched in the top 25% expression level genes, as compared to the total H3.3 nucleosomes or non-split H3.3 nucleosomes. Non-split H3.3 nucleosomes were enriched in the bottom 25% expression level genes. P values were calculated with chi-square test. ***P<0.001, **P<0.01, #P>0.1. (B) After normalization against the H3.3 occupancy, the split but not the non-split H3.3 nucleosomes were enriched at active genes. H3.3 nucleosomes at the entire genes were analyzed together.
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pgen-1003558-g005: H3.3 nucleosome splitting events are better markers for active transcription than H3.3 nucleosome occupancy.(A) Split H3.3 nucleosomes were enriched in the top 25% expression level genes, as compared to the total H3.3 nucleosomes or non-split H3.3 nucleosomes. Non-split H3.3 nucleosomes were enriched in the bottom 25% expression level genes. P values were calculated with chi-square test. ***P<0.001, **P<0.01, #P>0.1. (B) After normalization against the H3.3 occupancy, the split but not the non-split H3.3 nucleosomes were enriched at active genes. H3.3 nucleosomes at the entire genes were analyzed together.

Mentions: We next examined the relationship between the H3.3 nucleosome splitting events and transcriptional activity. For total H3.3 nucleosomes, split H3.3 nucleosomes (within the splitting index top 5%) and non-split H3.3 nucleosomes (within the splitting index bottom 5%) localized at genes, we individually examined their distribution profiles within different classes of genes that were categorized by their expression levels. Approximately 36% of total H3.3 nucleosomes and 25% of non-split H3.3 nucleosomes were localized at genes within the top 25% for expression levels. In contrast, 41% of the split H3.3 nucleosomes were located at these genes (Figure 5A), which is a significant difference with P value less than 0.0001 analyzed with Chi-square test. On the other hand, we found that 7% of total H3.3 nucleosomes and 5.5% of the split H3.3 nucleosomes were localized at genes within the bottom 25% for expression levels. However, 12% of non-split H3.3 nucleosomes were located at these genes (Figure 5A), which is also a significant enrichment with P value less than 0.0001. These data suggest that the split H3.3 nucleosomes were relatively enriched at active genes and non-split H3.3 nucleosomes were enriched at inactive genes.


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 are better markers for active transcription than H3.3 nucleosome occupancy.(A) Split H3.3 nucleosomes were enriched in the top 25% expression level genes, as compared to the total H3.3 nucleosomes or non-split H3.3 nucleosomes. Non-split H3.3 nucleosomes were enriched in the bottom 25% expression level genes. P values were calculated with chi-square test. ***P<0.001, **P<0.01, #P>0.1. (B) After normalization against the H3.3 occupancy, the split but not the non-split H3.3 nucleosomes were enriched at active genes. H3.3 nucleosomes at the entire genes were analyzed together.
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getmorefigures.php?uid=PMC3675017&req=5

pgen-1003558-g005: H3.3 nucleosome splitting events are better markers for active transcription than H3.3 nucleosome occupancy.(A) Split H3.3 nucleosomes were enriched in the top 25% expression level genes, as compared to the total H3.3 nucleosomes or non-split H3.3 nucleosomes. Non-split H3.3 nucleosomes were enriched in the bottom 25% expression level genes. P values were calculated with chi-square test. ***P<0.001, **P<0.01, #P>0.1. (B) After normalization against the H3.3 occupancy, the split but not the non-split H3.3 nucleosomes were enriched at active genes. H3.3 nucleosomes at the entire genes were analyzed together.
Mentions: We next examined the relationship between the H3.3 nucleosome splitting events and transcriptional activity. For total H3.3 nucleosomes, split H3.3 nucleosomes (within the splitting index top 5%) and non-split H3.3 nucleosomes (within the splitting index bottom 5%) localized at genes, we individually examined their distribution profiles within different classes of genes that were categorized by their expression levels. Approximately 36% of total H3.3 nucleosomes and 25% of non-split H3.3 nucleosomes were localized at genes within the top 25% for expression levels. In contrast, 41% of the split H3.3 nucleosomes were located at these genes (Figure 5A), which is a significant difference with P value less than 0.0001 analyzed with Chi-square test. On the other hand, we found that 7% of total H3.3 nucleosomes and 5.5% of the split H3.3 nucleosomes were localized at genes within the bottom 25% for expression levels. However, 12% of non-split H3.3 nucleosomes were located at these genes (Figure 5A), which is also a significant enrichment with P value less than 0.0001. These data suggest that the split H3.3 nucleosomes were relatively enriched at active genes and non-split H3.3 nucleosomes were enriched at inactive genes.

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