Genome-wide CIITA-binding profile identifies sequence preferences that dictate function versus recruitment.
Bottom Line: Nearly all CIITA-bound sites were within regions containing accessible chromatin, and CIITA's presence at these sites was associated with increased histone H3K27 acetylation, suggesting that CIITA's role at these non-regulated loci may be to poise the region for subsequent regulation.Computational genome-wide modeling of the CIITA bound XY box motifs provided constraints for sequences associated with CIITA-mediated gene regulation versus binding.These data therefore define the CIITA regulome in B cells and establish sequence specificities that predict activity for an essential regulator of the adaptive immune response.
Affiliation: Department of Microbiology and Immunology, Emory University, Atlanta, GA 30322, USA.Show MeSH
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Mentions: To examine how motif score and XY box length correlate, all 479 PWM CIITA-binding sites were analyzed (Figure 7A). Human MHC-II genes contained the highest scoring motifs with a total length ranging from 47 to 49 bp. CIITA sites outside of the MHC-II locus identified previously by ChIP-chip (26) also fell within a narrow window consistent with a defined spatial requirement of XY boxes (18). With the exception of MKNK2, all of Group I genes had spacing that matched the MHC-II phasing/periodicity previously described for the HLA-DRA XY box (18). Thus, the CIITA regulated genes display distinct spacing/phasing that separates this group of genes from those that recruit CIITA.
Affiliation: Department of Microbiology and Immunology, Emory University, Atlanta, GA 30322, USA.