CR Name:
Species:    Tissue or Cell: 

Chromatin Regulator

Alias

WDR5SWD3; BIG-3

External Links:

Wiki    GeneCards    NCBI    UniProt

Related histone modifications:

H3K4me2;H3K4me3;H3K4me1

Introduction

Full Name: WD repeat domain 5 . WDR5 belongs to the WD family of repeat proteins and is present in the human MLL and SET1 (hCOMPASS) histone H3 lysine 4 (H3K4) methyltransferase complexes, Ring1B/Rnf2 complexes, CHD8 chromatin remodeling complex, Ada Two-A-containing (ATAC) histone acetyltransferase complex, NRC interacting factor 1 (NIF-1) histone methyltransferase complex, and H1.2 transcriptional repressive complex, which are involved in transcriptional regulation, complex assembly and activity, proliferation and differentiation, development, and maintenance of the properties of the embryonic stem (ES) cells (1-19).

Function and Interaction

WDR5 is regarded as a transcriptional activator and is closely related to trimethylation of histone H3 lysine 4 (H3K4me3). WDR5 knockdown can lead to a decreased global level of H3K4me3, thus playing a role in activating Hox genes and in vertebrate development (1). It is also known to be essential for complex assembly and activity in an H3K4 methylation-independent manner (2-3). It has been suggested that CUL4B, which is often mutated in X-linked mental retardation (XLMR) patients, could ubiquitylate and degrade WDR5 in the nucleus, thus controlling neuronal gene expression (4). WDR5 interacts with VISA and recruits it in a viral infection-dependent fashion, thus playing an indispensable role in assembling a virus-induced VISA-associated complex and virus-induced activation of IRF3 and NF-κB (5). WDR5 is expressed in osteoblasts and is sufficient for dramatically accelerating the program of osteoblast differentiation, partly through the Wnt pathway. It is also expressed in proliferating and hypertrophic chondrocytes and is responsible for the differentiation and proliferation of chondrocytes (6-10). A study revealed that WDR5 can associate with pituitary homeobox 2 (Pitx2) and is thereby recruited to smooth muscle cell (SMC)-marker gene promoter regions. WDR5 suppression can specifically reduce H3K4me1 and H3K4me3 levels within the SMC-marker gene promoter region and consequentially inhibit the expression of these genes (11). WDR5 interacts with Oct4, which is a pluripotency transcription factor in embryonic stem (ES) cells, acting as a modulator of ES cell self-renewal, and is related to the undifferentiated state. Moreover, it is indispensable for the reprogramming of induced pluripotent stem (iPS) cells (12).

Disease Association

NA

ChIP-Seq data


SpeciesCell lineCell typeTissueDataDownloadSend to CistromeAnalysis FiguresComparisonReference
Homo sapiensBE2-CNoneNoneGSE70099 ,GSM1717083
Click  DownloadClickNA

ChIP-Seq data of related histone modifications


Products/SubstratesSpeciesCell lineCell typeTissueDataDownload Send to CistromeAnalysis FiguresReference
H3K4me3 Mus musculus V6.5 Embryonic Stem Cell Embryo GSE48172 ,GSM1171628 Bed     Big wiggle
Click   Download23934151
H3K4me3 Mus musculus V6.5 Embryonic Stem Cell Embryo GSE48172 ,GSM1171630 Bed     Big wiggle
Click   Download23934151
H3K4me3 Mus musculus V6.5 Embryonic Stem Cell Embryo GSE48172 ,GSM1171632 Bed     Big wiggle
Click   Download23934151
H3K4me3 Mus musculus E14 Embryonic Stem Cell Embryo GSE52071 ,GSM1258237 Bed     Big wiggle
Click   Download24423662
H3K4me3 Mus musculus NA Embryonic Stem Cell Embryo GSE52071 ,GSM1276704 Bed     Big wiggle
Click   Download24423662
H3K4me3 Mus musculus E14 Embryonic Stem Cell Embryo GSE52071 ,GSM1276705 Bed     Big wiggle
Click   Download24423662
H3K4me3 Mus musculus R1 Embryonic Stem Cell Embryo GSE53087 ,GSM1282137 Bed     Big wiggle
Click   Download24495580
H3K4me2 Mus musculus R1 Embryonic Stem Cell Embryo GSE53087 ,GSM1282138 Bed     Big wiggle
Click   Download24495580
H3K4me3 Mus musculus R1 Embryonic Stem Cell Embryo GSE53087 ,GSM1282139 Bed     Big wiggle
Click   Download24495580
H3K4me2 Mus musculus R1 Embryonic Stem Cell Embryo GSE53087 ,GSM1282140 Bed     Big wiggle
Click   Download24495580
H3K4me1 Homo sapiens SK-N-MC Epithelium Brain GSE61944 ,GSM1517539 Bed     Big wiggle
Click   Download25453903
H3K4me3 Homo sapiens SK-N-MC Epithelium Brain GSE61944 ,GSM1517541 Bed     Big wiggle
Click   Download25453903
H3K4me1 Homo sapiens SK-N-MC Epithelium Brain GSE61944 ,GSM1517548 Bed     Big wiggle
Click   Download25453903
H3K4me1 Homo sapiens A673 None None GSE61944 ,GSM1517564 Bed     Big wiggle
Click   Download25453903
H3K4me3 Homo sapiens BE2-C None None GSE70099 ,GSM1717082 Bed     Big wiggle
Click   DownloadNA
H3K4me3 Homo sapiens HEK293 Epithelium Embryonic Kidney GSE67673 ,GSM1853822 Bed     Big wiggle
Click   Download26368021
H3K4me3 Homo sapiens HEK293 Epithelium Embryonic Kidney GSE67673 ,GSM1853823 Bed     Big wiggle
Click   Download26368021
H3K4me3 Mus musculus R1 Embryonic Stem Cell Embryo GSE74268 ,GSM1915976 Bed     Big wiggle
Click   Download26628093
H3K4me3 Mus musculus XT67E1 Embryonic Stem Cell Embryo GSE15884 ,GSM397402 Bed     Big wiggle
Click   Download19581487
H3K4me3 Mus musculus XT67E1 Embryonic Stem Cell Embryo GSE15884 ,GSM397403 Bed     Big wiggle
Click   Download19581487
H3K4me3 Mus musculus XT67E1 Embryonic Stem Cell Embryo GSE15884 ,GSM397404 Bed     Big wiggle
Click   Download19581487
H3K4me3 Mus musculus C6 Embryonic Stem Cell Embryo GSE16893 ,GSM487545 Bed     Big wiggle
Click   Download20211137
H3K4me3 Mus musculus C6 Embryonic Stem Cell Embryo GSE16893 ,GSM487548 Bed     Big wiggle
Click   Download20211137
H3K4me2 Homo sapiens LNCaP Epithelium Prostate GSE20042 ,GSM503903 Bed     Big wiggle
Click   Download20208536
H3K4me2 Homo sapiens LNCaP Epithelium Prostate GSE20042 ,GSM503904 Bed     Big wiggle
Click   Download20208536
H3K4me2 Homo sapiens LNCaP Epithelium Prostate GSE20042 ,GSM503905 Bed     Big wiggle
Click   Download20208536
H3K4me3 Homo sapiens LNCaP Epithelium Prostate GSE20042 ,GSM503906 Bed     Big wiggle
Click   Download20208536
H3K4me3 Mus musculus TNGA Embryonic Stem Cell Embryo GSE23943 ,GSM590110 Bed     Big wiggle
Click   Download22541430
H3K4me3 Mus musculus C2C12 Myoblast Muscle GSE25549 ,GSM628005 Bed     Big wiggle
Click   Download22196887
H3K4me3 Mus musculus C2C12 Myoblast Muscle GSE25549 ,GSM628006 Bed     Big wiggle
Click   Download22196887
H3K4me2 Mus musculus NA Embryonic Stem Cell Embryo GSE25533 ,GSM632035 Bed     Big wiggle
Click   Download22179133
H3K4me1 Homo sapiens NHEK Keratinocyte Skin GSE26320 ,GSM646462 Bed     Big wiggle
Click   Download21441907
H3K4me1 Homo sapiens NHEK Keratinocyte Skin GSE26320 ,GSM646463 Bed     Big wiggle
Click   Download21441907
H3K4me2 Homo sapiens NHEK Keratinocyte Skin GSE26320 ,GSM646464 Bed     Big wiggle
Click   Download21441907
H3K4me2 Homo sapiens NHEK Keratinocyte Skin GSE26320 ,GSM646465 Bed     Big wiggle
Click   Download21441907
H3K4me3 Homo sapiens NHEK Keratinocyte Skin GSE26320 ,GSM646467 Bed     Big wiggle
Click   Download21441907
H3K4me3 Mus musculus E14 Embryonic Stem Cell Embryo GSE26136 ,GSM651193 Bed     Big wiggle
Click   Download21335234
H3K4me3 Homo sapiens LNCaP Epithelium Prostate GSE27824 ,GSM686935 Bed     Big wiggle
Click   Download21572438
H3K4me2 Mus musculus NA Embryonic Stem Cell Embryo GSE33252 ,GSM686995 Bed     Big wiggle
Click   Download21655081
H3K4me2 Mus musculus C2C12 Myoblast Muscle GSE25308 ,GSM721290 Bed     Big wiggle
Click   Download21551099
H3K4me2 Mus musculus C2C12 Myoblast Muscle GSE25308 ,GSM721291 Bed     Big wiggle
Click   Download21551099
H3K4me2 Homo sapiens NHEK Keratinocyte Skin GSE29611 ,GSM733686 Bed     Big wiggle
Click   Download22955616
H3K4me1 Homo sapiens NHEK Keratinocyte Skin GSE29611 ,GSM733698 Bed     Big wiggle
Click   Download22955616
H3K4me3 Homo sapiens NHEK Keratinocyte Skin GSE29611 ,GSM733720 Bed     Big wiggle
Click   Download22955616
H3K4me2 Mus musculus NA Embryonic Stem Cell Embryo GSE30203 ,GSM747544 Bed     Big wiggle
Click   Download22170606
H3K4me3 Mus musculus C2C12 Myoblast Muscle GSE33024 ,GSM818946 Bed     Big wiggle
Click   Download22085726
H3K4me2 Mus musculus C2C12 Myoblast Muscle GSE33227 ,GSM822511 Bed     Big wiggle
Click   Download24714595
H3K4me3 Mus musculus CMTi-1 Embryonic Stem Cell Embryo GSE34483 ,GSM849941 Bed     Big wiggle
Click   Download23260488
H3K4me2 Mus musculus E14 Embryonic Stem Cell Embryo GSE38596 ,GSM881353 Bed     Big wiggle
Click   Download22682255
H3K4me2 Mus musculus E14 Embryonic Stem Cell Embryo GSE38596 ,GSM881361 Bed     Big wiggle
Click   Download22682255
H3K4me2 Mus musculus E14 Embryonic Stem Cell Embryo GSE38596 ,GSM881370 Bed     Big wiggle
Click   Download22682255
H3K4me3 Mus musculus R1 Embryonic Stem Cell Embryo GSE36294 ,GSM886518 Bed     Big wiggle
Click   Download24381111
H3K4me2 Mus musculus R1 Embryonic Stem Cell Embryo GSE36294 ,GSM886531 Bed     Big wiggle
Click   Download24381111
H3K4me3 Mus musculus TC1 Embryonic Stem Cell Embryo GSE37776 ,GSM928131 Bed     Big wiggle
Click   Download22666422
H3K4me3 Mus musculus 3.2N Embryonic Stem Cell Embryo GSE37776 ,GSM928132 Bed     Big wiggle
Click   Download22666422
H3K4me3 Homo sapiens NHEK Keratinocyte Skin GSE35583 ,GSM945175 Bed     Big wiggle
Click   Download22955617
H3K4me3 Homo sapiens LNCaP Epithelium Prostate GSE35583 ,GSM945240 Bed     Big wiggle
Click   Download22955617
H3K4me3 Homo sapiens HEK293 Epithelium Embryonic Kidney GSE35583 ,GSM945288 Bed     Big wiggle
Click   Download22955617
H3K4me3 Mus musculus NA Embryonic Stem Cell Embryo GSE39472 ,GSM969829 Bed     Big wiggle
Click   Download22826230
H3K4me3 Mus musculus NA Embryonic Stem Cell Embryo GSE39472 ,GSM969830 Bed     Big wiggle
Click   Download22826230
H3K4me3 Mus musculus E36 Embryonic Stem Cell Embryo GSE39496 ,GSM970227 Bed     Big wiggle
Click   Download24289921
H3K4me3 Mus musculus E36 Embryonic Stem Cell Embryo GSE39496 ,GSM970228 Bed     Big wiggle
Click   Download24289921

Notice: For bigwiggle or bed file download, if the browser cannot automatically download the file, users can right click the hyperlink and then click the "Save link as..." button, which will automatically redirect to download dialogue box, or click the "Copy link address" button and access the website in a new tab page. For data analysis in Cistrome, users should first login into the Cistrome website, then press the "Send Bed" or "Send Big wiggle" button. For data download by Cistrome, users can follow this tutorial.

References

1. Wysocka, J., Swigut, T., Milne, T.A., Dou, Y.L., Zhang, X., Burlingame, A.L., Roeder, R.G., Brivanlou, A.H. and Allis, C.D. (2005) WDR5 associates with histone H3 methylated at K4 and is essential for H3K4 methylation and vertebrate development. Cell, 121, 859-872.
2. Trievel, R.C. and Shilatifard, A. (2009) WDR5, a complexed protein. Nature Structural & Molecular Biology, 16, 678-680.
3. Dou, Y.L., Milne, T.A., Ruthenburg, A.J., Lee, S., Lee, J.W., Verdine, G.L., Allis, C.D. and Roeder, R.G. (2006) Regulation of MLL1 H3K4 methyltransferase activity by its core components. Nature Structural & Molecular Biology, 13, 713-719.
4. Nakagawa, T. and Xiong, Y. (2011) X-Linked Mental Retardation Gene CUL4B Targets Ubiquitylation of H3K4 Methyltransferase Component WDR5 and Regulates Neuronal Gene Expression. Mol Cell, 43, 381-391.
5. Wang, Y.Y., Liu, L.J., Zhong, B., Liu, T.T., Li, Y., Yang, Y., Ran, Y., Li, S., Tien, P. and Shu, H.B. (2010) WDR5 is essential for assembly of the VISA-associated signaling complex and virus-triggered IRF3 and NF-kappa B activation. P Natl Acad Sci USA, 107, 815-820.
6. Gori, F., Divieti, P. and Demay, M.B. (2001) Cloning and characterization of a novel WD-40 repeat protein that dramatically accelerates osteoblastic differentiation. J Biol Chem, 276, 46515-46522.
7. Gori, F. and Demay, M.B. (2004) BIG-3, a novel WD-40 repeat protein, is expressed in the developing growth plate and accelerates chondrocyte differentiation in vitro. Endocrinology, 145, 1050-1054.
8. Gori, F., Friedman, L.G. and Demay, M.B. (2006) Wdr5, a WD-40 protein, regulates osteoblast differentiation during embryonic bone development. Developmental Biology, 295, 498-506.
9. Zhu, E.D., Demay, M.B. and Gori, F. (2008) Wdr5 is essential for osteoblast differentiation. J Biol Chem, 283, 7361-7367.
10. Gori, F., Zhu, E.D. and Demay, M.B. (2009) Perichondrial expression of Wdr5 regulates chondrocyte proliferation and differentiation. Developmental Biology, 329, 36-43.
11. Gan, Q., Thiebaud, P., Theze, N., Jin, L., Xu, G.F., Grant, P. and Owens, G.K. (2011) WD Repeat-containing Protein 5, a Ubiquitously Expressed Histone Methyltransferase Adaptor Protein, Regulates Smooth Muscle Cell-selective Gene Activation through Interaction with Pituitary Homeobox 2. J Biol Chem, 286, 21853-21864.
12. Ang, Y.S., Tsai, S.Y., Lee, D.F., Monk, J., Su, J., Ratnakumar, K., Ding, J.J., Ge, Y.C., Darr, H., Chang, B. et al. (2011) Wdr5 Mediates Self-Renewal and Reprogramming via the Embryonic Stem Cell Core Transcriptional Network. Cell, 145, 183-197.
13. Dou, Y., Milne, T.A., Tackett, A.J., Smith, E.R., Fukuda, A., Wysocka, J., Allis, C.D., Chait, B.T., Hess, J.L. and Roeder, R.G. (2005) Physical association and coordinate function of the H3 K4 methyltransferase MLL1 and the H4 K16 acetyltransferase MOF. Cell, 121, 873-885.
14. Ruthenburg, A.J., Wang, W., Graybosch, D.M., Li, H., Allis, C.D., Patel, D.J. and Verdine, G.L. (2006) Histone H3 recognition and presentation by the WDR5 module of the MLL1 complex. Nat Struct Mol Biol, 13, 704-712.
15. Sanchez, C., Sanchez, I., Demmers, J.A., Rodriguez, P., Strouboulis, J. and Vidal, M. (2007) Proteomics analysis of Ring1B/Rnf2 interactors identifies a novel complex with the Fbxl10/Jhdm1B histone demethylase and the Bcl6 interacting corepressor. Mol Cell Proteomics, 6, 820-834.
16. Wang, Y.L., Faiola, F., Xu, M.Y., Pan, S.Q. and Martinez, E. (2008) Human ATAC Is a GCN5/PCAF-containing Acetylase Complex with a Novel NC2-like Histone Fold Module That Interacts with the TATA-binding Protein. J Biol Chem, 283, 33808-33815.
17. Kim, K., Choi, J., Heo, K., Kim, H., Levens, D., Kohno, K., Johnson, E.M., Brock, H.W. and An, W. (2008) Isolation and characterization of a novel H1.2 complex that acts as a repressor of p53-mediated transcription. J Biol Chem, 283, 9113-9126.
18. Garapaty, S., Xu, C.F., Trojer, P., Mahajan, M.A., Neubert, T.A. and Samuels, H.H. (2009) Identification and Characterization of a Novel Nuclear Protein Complex Involved in Nuclear Hormone Receptor-mediated Gene Regulation. J Biol Chem, 284, 7542-7552.
19. Smith, T.F., Gaitatzes, C., Saxena, K. and Neer, E.J. (1999) The WD repeat: a common architecture for diverse functions. Trends Biochem Sci, 24, 181-185.

Figure Gallery

pix pix pix pix pix pix

About Chromatin Regulator

Chromatin Regulator Cistrome
is a unique database integrating curated information of CRs, CR ChIP-seq datasets, CR related HM ChIP-seq datasets, and analysis of the relationship between CRs and HMs ChIP-seq pairs in human and mouse.

Contact

houshuang [at] tongji dot edu dot cn