Last update 01 Nov 2024

WDR5

Last update 01 Nov 2024

Basic Info

Synonyms

BIG3, BMP2-induced 3-kb gene protein, CFAP89

+ [6]

Introduction

Contributes to histone modification (PubMed:19131338, PubMed:19556245, PubMed:19103755, PubMed:20018852, PubMed:16600877, PubMed:16829960). May position the N-terminus of histone H3 for efficient trimethylation at 'Lys-4' (PubMed:16829960). As part of the MLL1/MLL complex it is involved in methylation and dimethylation at 'Lys-4' of histone H3 (PubMed:19556245). H3 'Lys-4' methylation represents a specific tag for epigenetic transcriptional activation (PubMed:18840606). As part of the NSL complex it may be involved in acetylation of nucleosomal histone H4 on several lysine residues (PubMed:19103755, PubMed:20018852). May regulate osteoblasts differentiation (By similarity). In association with RBBP5 and ASH2L, stimulates the histone methyltransferase activities of KMT2A, KMT2B, KMT2C, KMT2D, SETD1A and SETD1B (PubMed:21220120, PubMed:22266653).

Drugs associated with WDR5

WDR5-0103

Target

MLL1 x WDR5

Mechanism

MLL1 inhibitors [+1]

Active Org.

Structural Genomics Consortium

Originator Org.

Structural Genomics Consortium

Active Indication

Leukemia

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

DC_M5_2

Target

MLL1 x WDR5

Mechanism

MLL1 inhibitors [+1]

Active Org.

Shanghai Institute of Materia Medica Chinese Academy of Sci

Originator Org.

Shanghai Institute of Materia Medica Chinese Academy of Sci

Active Indication

Leukemia

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

MM-589

Target

MLL1 x WDR5

Mechanism

MLL1 inhibitors [+1]

Active Org.

University of Michigan

Originator Org.

University of Michigan

Active Indication

Leukemia

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with WDR5

100 Translational Medicine associated with WDR5

0 Patents (Medical) associated with WDR5

479

Literatures (Medical) associated with WDR5

01 Dec 2024·Molecular Genetics and Genomics

lncCPSET1 acts as a scaffold for MLL2/COMPASS to regulate Bmp4 and promote the formation of chicken primordial germ cells

Article

Author: Zuo, Qisheng ; Jin, Kai ; Zhang, Chen ; Li, Bichun ; Ding, Ying

Primordial germ cells (PGCs) are the ancestors of female and male germ cells. Recent studies have shown that long non-coding RNA (lncRNA) and histone methylation are key epigenetic factors affecting PGC formation; however, their joint regulatory mechanisms have rarely been studied. Here, we explored the mechanism by which lncCPSET1 and H3K4me2 synergistically regulate the formation of chicken PGCs for the first time. Combined with chromatin immunoprecipitation (CHIP) sequencing and RNA-seq of PGCs transfected with the lncCPSET1 overexpression vector, GO annotation and KEGG enrichment analysis revealed that Wnt and TGF-β signaling pathways were significantly enriched, and Fzd2, Id1, Id4, and Bmp4 were identified as candidate genes. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) showed that ASH2L, DPY30, WDR5, and RBBP5 overexpression significantly increased the expression of Bmp4, which was up-regulated after lncCPSET1 overexpression as well. It indicated that Bmp4 is a target gene co-regulated by lncCPSET1 and MLL2/COMPASS. Interestingly, co-immunoprecipitation results showed that ASH2L, DPY30 and WDR5 combined and RBBP5 weakly combined with DPY30 and WDR5. lncCPSET1 overexpression significantly increased Dpy30 expression and co-immunoprecipitation showed that interference/overexpression of lncCPSET1 did not affect the binding between the proteins in the complexes, but interference with lncCPSET1 inhibited DPY30 expression, which was confirmed by RNA immunoprecipitation that lncCPSET1 binds to DPY30. Additionally, CHIP-qPCR results showed that DPY30 enriched in the Bmp4 promoter region promoted its transcription, thus promoting the formation of PGCs. This study demonstrated that lncCPSET1 and H3K4me2 synergistically promote PGC formation, providing a reference for the study of the regulatory mechanisms between lncRNA and histone methylation, as well as a molecular basis for elucidating the formation mechanism of PGCs in chickens.

09 Oct 2024·Journal of the American Chemical Society

WDR5 Binding to Histone Serotonylation Is Driven by an Edge–Face Aromatic Interaction with Unexpected Electrostatic Effects

Article

Author: Wilkinson, Jake R. ; Treacy, Joseph W. ; Waters, Marcey L. ; Schomburg, Noah K. ; Houk, K. N. ; Henriksen, Hanne C. ; Kean, Kelsey M. ; Travis, Christopher R.

Histone serotonylation has emerged as a key post-translational modification. WDR5 preferentially binds to serotonylated histone 3 (H3), and this binding event has been associated with tumorigenesis. Herein, we utilize genetic code expansion, structure-activity relationship studies, and computation to study an edge-face aromatic interaction between WDR5 Phe149 and serotonin on H3 that is key to this protein-protein interaction. We find experimentally that this edge-face aromatic interaction is unaffected by modulating the electrostatics of the face component but is weakened by electron-withdrawing substituents on the edge component. Overall, these results elucidate that this interaction is governed by van der Waals forces as well as electrostatics of the edge ring, a result that clarifies discrepancies among previous theoretical models and model system studies of this interaction type. This is the first evaluation of the driving force of an edge-face aromatic interaction at a protein-protein interface and provides a key benchmark for the nature of these understudied interactions that are abundant in the proteome.

25 Sep 2024·Dental Materials Journal

Biomimetic concentric microgrooved titanium surfaces influence bone marrow-derived mesenchymal stem cell osteogenic differentiation via H3K4 trimethylation epigenetic regulation.

Article

Author: Xu, Zhiqiang ; Gao, Yuerong ; Chen, Yan ; Wang, Hong ; Weng, Xinze ; Guan, Xin ; Wu, Qinglin ; Huang, Yanling ; Mao, Shunjie ; Lai, Yingzhen

Material surface micromorphology can modulate cellular behavior and promote osteogenic differentiation through cytoskeletal rearrangement. Bone reconstruction requires precise regulation of gene expression in cells, a process governed by epigenetic mechanisms such as histone modifications, DNA methylation, and chromatin remodeling. We constructed osteon-mimetic concentric microgrooved titanium surfaces with different groove sizes and cultured bone marrow-derived mesenchymal stem cells (BMSCs) on the material surfaces to study how they regulate cell biological behavior and osteogenic differentiation through epigenetics. We found that the cells arranged in concentric circles along the concentric structure in the experimental group, and the concentric microgrooved surface did not inhibit cell proliferation. The results of a series of osteogenic differentiation experiments showed that the concentric microgrooves facilitated calcium deposition and promoted osteogenic differentiation of the BMSCs. Concentric microgrooved titanium surfaces that were 30 μm wide and 10 μm deep promoted osteogenic differentiation of BMSC by increasing WDR5 expression via H3K4 trimethylation upregulation.

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WDR5

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