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BCL6 orchestrates Tfh cell differentiation via multiple distinct mechanisms.

Hatzi K, Nance JP, Kroenke MA, Bothwell M, Haddad EK, Melnick A, Crotty S - J. Exp. Med. (2015)

Bottom Line: BCL6 primarily acts as a repressor in Tfh cells, and BCL6 binding was associated with control of Tfh cell migration and repression of alternative cell fates.We show that BCL6 can directly bind AP1, and BCL6 depends on AP1 for recruitment to BCL6-binding sites with AP1 motifs, suggesting that BCL6 subverts AP1 activity.These findings reveal that BCL6 has broad and multifaceted effects on Tfh biology and provide insight into how this master regulator mediates distinct cell context-dependent phenotypes.

View Article: PubMed Central - HTML - PubMed

Affiliation: Division of Hematology and Medical Oncology, Weill Cornell Medical College, Cornell University, New York, NY 10065.

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Comparison of specialized BCL6 GC Tfh and GC B cell targeted chromatin landscape. Heat maps of read density profiles of BCL6, H3K4me1, and H3K27ac ChIP-seq in GC B and Tfh cells surrounding BCL6 peaks outside promoters. Maps were centered at the BCL6 peak summit and were separated in peaks common to GC B and T cells, GC Tfh-only peaks, and GC B-only peaks. T cell ChIP-seq data are from two experiments, comprising primary CD4 T cells from three human donors. Values were normalized to the total number of reads.
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fig5: Comparison of specialized BCL6 GC Tfh and GC B cell targeted chromatin landscape. Heat maps of read density profiles of BCL6, H3K4me1, and H3K27ac ChIP-seq in GC B and Tfh cells surrounding BCL6 peaks outside promoters. Maps were centered at the BCL6 peak summit and were separated in peaks common to GC B and T cells, GC Tfh-only peaks, and GC B-only peaks. T cell ChIP-seq data are from two experiments, comprising primary CD4 T cells from three human donors. Values were normalized to the total number of reads.

Mentions: Because most of the cell context–dependent BCL6 targets occur outside gene promoters, we examined the chromatin architecture surrounding these sites. We found that the chromatin marks H3K4me1 and H3K27ac, which are associated with enhancers, were selectively enriched in the GC B-only and GC Tfh-only BCL6 loci in B and T cells, respectively, but were largely absent in the opposite cell type (Fig. 5). On the contrary, both of these histone marks were enriched in the smaller subset of common T-B peaks both in T and in B cells. This result highlights that the role of BCL6 is associated with unique cell context–specific chromatin landscapes.


BCL6 orchestrates Tfh cell differentiation via multiple distinct mechanisms.

Hatzi K, Nance JP, Kroenke MA, Bothwell M, Haddad EK, Melnick A, Crotty S - J. Exp. Med. (2015)

Comparison of specialized BCL6 GC Tfh and GC B cell targeted chromatin landscape. Heat maps of read density profiles of BCL6, H3K4me1, and H3K27ac ChIP-seq in GC B and Tfh cells surrounding BCL6 peaks outside promoters. Maps were centered at the BCL6 peak summit and were separated in peaks common to GC B and T cells, GC Tfh-only peaks, and GC B-only peaks. T cell ChIP-seq data are from two experiments, comprising primary CD4 T cells from three human donors. Values were normalized to the total number of reads.
© Copyright Policy - openaccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4387288&req=5

fig5: Comparison of specialized BCL6 GC Tfh and GC B cell targeted chromatin landscape. Heat maps of read density profiles of BCL6, H3K4me1, and H3K27ac ChIP-seq in GC B and Tfh cells surrounding BCL6 peaks outside promoters. Maps were centered at the BCL6 peak summit and were separated in peaks common to GC B and T cells, GC Tfh-only peaks, and GC B-only peaks. T cell ChIP-seq data are from two experiments, comprising primary CD4 T cells from three human donors. Values were normalized to the total number of reads.
Mentions: Because most of the cell context–dependent BCL6 targets occur outside gene promoters, we examined the chromatin architecture surrounding these sites. We found that the chromatin marks H3K4me1 and H3K27ac, which are associated with enhancers, were selectively enriched in the GC B-only and GC Tfh-only BCL6 loci in B and T cells, respectively, but were largely absent in the opposite cell type (Fig. 5). On the contrary, both of these histone marks were enriched in the smaller subset of common T-B peaks both in T and in B cells. This result highlights that the role of BCL6 is associated with unique cell context–specific chromatin landscapes.

Bottom Line: BCL6 primarily acts as a repressor in Tfh cells, and BCL6 binding was associated with control of Tfh cell migration and repression of alternative cell fates.We show that BCL6 can directly bind AP1, and BCL6 depends on AP1 for recruitment to BCL6-binding sites with AP1 motifs, suggesting that BCL6 subverts AP1 activity.These findings reveal that BCL6 has broad and multifaceted effects on Tfh biology and provide insight into how this master regulator mediates distinct cell context-dependent phenotypes.

View Article: PubMed Central - HTML - PubMed

Affiliation: Division of Hematology and Medical Oncology, Weill Cornell Medical College, Cornell University, New York, NY 10065.

Show MeSH
Related in: MedlinePlus