WDR5 explained

WD repeat-containing protein 5 is a protein that in humans is encoded by the WDR5 gene.^{[1] [2]}

This gene encodes a member of the WD repeat protein family. WD repeats are minimally conserved regions of approximately 40 amino acids typically bracketed by gly-his and trp-asp (GH-WD), which may facilitate formation of heterotrimeric or multiprotein complexes. Members of this family are involved in a variety of cellular processes, including cell cycle progression, signal transduction, apoptosis, and gene regulation. This protein contains 7 WD repeats. Alternatively spliced transcript variants encoding the same protein have been identified.^[2]

Interactions

WDR5 has been shown to interact with Host cell factor C1^{[3] [4]} and MLL.^[3] It also interacts with the long non-coding RNA HOTTIP and to the lncRNA NeST.^{[5] [6]} WDR5 is a key determinant for MYC recruitment to chromatin^[7]

Further reading

• Strausberg RL, Feingold EA, Grouse LH, etal . Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. . Proc. Natl. Acad. Sci. U.S.A. . 99 . 26 . 16899–903 . 2003 . 12477932 . 10.1073/pnas.242603899 . 139241 . 2002PNAS...9916899M . free .
• Wysocka J, Myers MP, Laherty CD, etal . Human Sin3 deacetylase and trithorax-related Set1/Ash2 histone H3-K4 methyltransferase are tethered together selectively by the cell-proliferation factor HCF-1. . Genes Dev. . 17 . 7 . 896–911 . 2003 . 12670868 . 10.1101/gad.252103 . 196026 .
• Gori F, Demay MB . BIG-3, a novel WD-40 repeat protein, is expressed in the developing growth plate and accelerates chondrocyte differentiation in vitro. . Endocrinology . 145 . 3 . 1050–4 . 2004 . 14657013 . 10.1210/en.2003-1314 . free .
• Ota T, Suzuki Y, Nishikawa T, etal . Complete sequencing and characterization of 21,243 full-length human cDNAs. . Nat. Genet. . 36 . 1 . 40–5 . 2004 . 14702039 . 10.1038/ng1285 . free .
• Yokoyama A, Wang Z, Wysocka J, etal . Leukemia proto-oncoprotein MLL forms a SET1-like histone methyltransferase complex with menin to regulate Hox gene expression. . Mol. Cell. Biol. . 24 . 13 . 5639–49 . 2004 . 15199122 . 10.1128/MCB.24.13.5639-5649.2004 . 480881 .
• Gerhard DS, Wagner L, Feingold EA, etal . The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). . Genome Res. . 14 . 10B . 2121–7 . 2004 . 15489334 . 10.1101/gr.2596504 . 528928 .
• Andersen JS, Lam YW, Leung AK, etal . Nucleolar proteome dynamics. . Nature . 433 . 7021 . 77–83 . 2005 . 15635413 . 10.1038/nature03207 . 2005Natur.433...77A . 4344740 .
• Wysocka J, Swigut T, Milne TA, etal . WDR5 associates with histone H3 methylated at K4 and is essential for H3 K4 methylation and vertebrate development. . Cell . 121 . 6 . 859–72 . 2005 . 15960974 . 10.1016/j.cell.2005.03.036 . 17521631 . free .
• Dou Y, Milne TA, Tackett AJ, etal . Physical association and coordinate function of the H3 K4 methyltransferase MLL1 and the H4 K16 acetyltransferase MOF. . Cell . 121 . 6 . 873–85 . 2005 . 15960975 . 10.1016/j.cell.2005.04.031 . 14717470 . free .
• Rual JF, Venkatesan K, Hao T, etal . Towards a proteome-scale map of the human protein-protein interaction network. . Nature . 437 . 7062 . 1173–8 . 2005 . 16189514 . 10.1038/nature04209 . 2005Natur.437.1173R . 4427026 .
• Gori F, Friedman L, Demay MB . Wdr5, a novel WD repeat protein, regulates osteoblast and chondrocyte differentiation in vivo. . Journal of Musculoskeletal & Neuronal Interactions . 5 . 4 . 338–9 . 2006 . 16340128 .
• Lim J, Hao T, Shaw C, etal . A protein-protein interaction network for human inherited ataxias and disorders of Purkinje cell degeneration. . Cell . 125 . 4 . 801–14 . 2006 . 16713569 . 10.1016/j.cell.2006.03.032 . 13709685 . free .
• Ruthenburg AJ, Wang W, Graybosch DM, etal . Histone H3 recognition and presentation by the WDR5 module of the MLL1 complex. . Nat. Struct. Mol. Biol. . 13 . 8 . 704–12 . 2006 . 16829959 . 10.1038/nsmb1119 . 4698793 .
• Couture JF, Collazo E, Trievel RC . Molecular recognition of histone H3 by the WD40 protein WDR5. . Nat. Struct. Mol. Biol. . 13 . 8 . 698–703 . 2006 . 16829960 . 10.1038/nsmb1116 . 26165068 .
• Dou Y, Milne TA, Ruthenburg AJ, etal . Regulation of MLL1 H3K4 methyltransferase activity by its core components. . Nat. Struct. Mol. Biol. . 13 . 8 . 713–9 . 2006 . 16878130 . 10.1038/nsmb1128 . 12849159 .
• Schuetz A, Allali-Hassani A, Martín F, etal . Structural basis for molecular recognition and presentation of histone H3 by WDR5. . EMBO J. . 25 . 18 . 4245–52 . 2006 . 16946699 . 10.1038/sj.emboj.7601316 . 1570438 .
• Ewing RM, Chu P, Elisma F, etal . Large-scale mapping of human protein-protein interactions by mass spectrometry. . Mol. Syst. Biol. . 3 . 1. 89 . 2007 . 17353931 . 10.1038/msb4100134 . 1847948 .
• Bryan AF, Wang J, Howard GC etal . WDR5 is a conserved regulator of protein synthesis gene expression. . Nucleic Acids Research . 48 . 6. 2924–2941 . 2020 . 31996893. 10.1093/nar/gkaa051 . 7102967. free .

Notes and References

1. Gori F, Divieti P, Demay MB . Cloning and characterization of a novel WD-40 repeat protein that dramatically accelerates osteoblastic differentiation . J Biol Chem . 276 . 49 . 46515–22 . Dec 2001 . 11551928 . 10.1074/jbc.M105757200 . free .
2. Web site: Entrez Gene: WDR5 WD repeat domain 5.
3. Yokoyama . Akihiko . Wang Zhong . Wysocka Joanna . Sanyal Mrinmoy . Aufiero Deborah J . Kitabayashi Issay . Herr Winship . Cleary Michael L . Jul 2004 . Leukemia proto-oncoprotein MLL forms a SET1-like histone methyltransferase complex with menin to regulate Hox gene expression . Mol. Cell. Biol. . 24 . 13 . 5639–49 . 0270-7306. 15199122 . 10.1128/MCB.24.13.5639-5649.2004 . 480881 .
4. Wysocka . Joanna . Myers Michael P . Laherty Carol D . Eisenman Robert N . Herr Winship . Apr 2003 . Human Sin3 deacetylase and trithorax-related Set1/Ash2 histone H3-K4 methyltransferase are tethered together selectively by the cell-proliferation factor HCF-1 . Genes Dev. . 17 . 7 . 896–911 . 0890-9369. 12670868 . 10.1101/gad.252103 . 196026 .
5. Wells . Alexandria C. . Pobezinskaya . Elena L. . Pobezinsky . Leonid A. . April 2020 . Non-coding RNAs in CD8 T cell biology . Molecular Immunology . 120 . 67–73 . 10.1016/j.molimm.2020.01.023 . 1872-9142 . 7093237 . 32085976.
6. Wang KC, Yang YW, Liu B, Sanyal A, Corces-Zimmerman R, Chen Y, etal . A long noncoding RNA maintains active chromatin to coordinate homeotic gene expression. . Nature . 2011 . 472 . 7341 . 120–4 . 21423168 . 10.1038/nature09819 . 3670758. 2011Natur.472..120W .
7. Thomas . L. R. . Tansey . W. P. . 2015 . Interaction with WDR5 Promotes Target Gene Recognition and Tumorigenesis by MYC . Molecular Cell . 58 . 3. 1–13 . 10.1016/j.molcel.2015.02.028 . 25818646 . 4427524.