Molecular Basis of Histone Tail Recognition by Human TIP5 PHD Finger and Bromodomain of the Chromatin Remodeling Complex NoRC

Binding of the chromatin remodeling complex NoRC to RNA complementary to the rDNA promoter mediates transcriptional repression. TIP5, the largest subunit of NoRC, is involved in recruitment to rDNA by interactions with promoter-bound TTF-I, pRNA, and acetylation of H4K16. TIP5 domains that recognize posttranslational modifications on histones are essential for recruitment of NoRC to chromatin, but how these reader modules recognize site-specific histone tails has remained elusive. Here, we report crystal structures of PHD zinc finger and bromodomains from human TIP5 and BAZ2B in free form and bound to H3 and/or H4 histones. PHD finger functions as an independent structural module in recognizing unmodified H3 histone tails, and the bromodomain prefers H3 and H4 acetylation marks followed by a key basic residue, KacXXR. Further low-resolution analyses of PHD-bromodomain modules provide molecular insights into their trans histone tail recognition, required for nucleosome recruitment and transcriptional repression of the NoRC complex. [Display omitted] •TIP5 and BAZ2B PHD zinc fingers recognize unmodified H3K4•TIP5 and BAZ2B bromodomain recognize H4K16ac and H3K14ac with specific motif KacXXR•Cocrystal structures of individual domains define the basis for histone recognition•SAXS data for BAZ2B suggest independent PTM recognition Reader domains of chromatin remodeling complexes NoRC/BAZ2B recognize posttranslationally modified histone tails. Tallant et al. reveal the molecular basis for binding specificity of PHD fingers to unmodified H3K4 and bromodomains to a Kac-X-X-R pattern, occurring through structurally independent recognition.