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Publication Abstract from PubMed

Pygo proteins promote Armadillo- and beta-catenin-dependent transcription, by relieving Groucho-dependent repression of Wnt targets. Their PHD fingers bind histone H3 tail methylated at lysine 4, and to the HD1 domain of their Legless/BCL9 cofactors, linking Pygo to Armadillo/beta-catenin. Intriguingly, fly Pygo orthologs exhibit a tryptophan > phenylalanine substitution in their histone pocket-divider which reduces their affinity for histones. Here, we use X-ray crystallography and NMR, to discover a conspicuous groove bordering this phenylalanine in the Drosophila PHD-HD1 complex-a semi-aromatic cage recognizing asymmetrically methylated arginine 2 (R2me2a), a chromatin mark of silenced genes. Our structural model of the ternary complex reveals a distinct mode of dimethylarginine recognition, involving a polar interaction between R2me2a and its groove, the structural integrity of which is crucial for normal tissue patterning. Notably, humanized fly Pygo derepresses Notch targets, implying an inherent Notch-related function of classical Pygo orthologs, disabled in fly Pygo, which thus appears dedicated to Wnt signaling.

Evolutionary Adaptation of the Fly Pygo PHD Finger toward Recognizing Histone H3 Tail Methylated at Arginine 2.,Miller TC, Mieszczanek J, Sanchez-Barrena MJ, Rutherford TJ, Fiedler M, Bienz M Structure. 2013 Oct 30. pii: S0969-2126(13)00364-X. doi:, 10.1016/j.str.2013.09.013. PMID:24183574^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.