On WD40 proteins: propelling our knowledge of transcriptional control?
A direct effect of post-translational modifications (PTMs) on nucleosomes is the formation of a dynamic platform able to assemble the transcriptional machinery and to recruit chromatin modifiers. The histone code hypothesis suggests that histone PTMs can act as binding sites for chromatin readers and effector proteins, such as the bromodomains, that selectively interact with acetylated lysines, or the "Royal family" and the PHD finger domains, which are able to recognize methylated arginines and lysines. In this review we will discuss recent data describing the function of WD40 proteins as a new class of histone readers, with particular emphasis on the ones able to recognize methylated arginine and lysine residues. We will discuss how WDR5, a classical seven-bladed WD40 propeller, is able to bind with similar affinities both the catalytic subunit of the Trithorax-like complexes, and the histone H3 tail either unmodified or symmetrically dimethylated on arginine 2 (H3R2me2s). Furthermore, we will speculate on how these mutually exclusive interactions of WDR5 may play a role in mediating different degrees of H3K4 methylations at both promoters and distal regulatory sites. Finally, we will summarize recent literature elucidating how other WD40 proteins such as NURF55, EED and LRWD1 recognize methylated histone tails, highlighting similarities and differences among them.
Institute of Molecular and Cell Biology, Singapore, Singapore.
Valentina
V
Migliori
Marina
M
Mapelli
Ernesto
E
Guccione
D000818:Animals; D002843:Chromatin / Q000235:genetics / Q000378:metabolism; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics / Q000378:metabolism; D042421:Histone Code; D011495:Histone-Lysine N-Methyltransferase / Q000235:genetics / Q000378:metabolism*; D006657:Histones / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D011484:Protein-Arginine N-Methyltransferases / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic
D002843:Chromatin; D002868:Chromosomal Proteins, Non-Histone; D006657:Histones; D047908:Intracellular Signaling Peptides and Proteins; C502547:WDR5 protein, human; D011484:Protein-Arginine N-Methyltransferases; D011495:Histone-Lysine N-Methyltransferase