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The histone H3 lysine 4 presenter WDR5 induces N-Myc target gene transcription and promotes neuroblastoma [ChIP-Seq]

ABSTRACT: WDR5 is an important co-factor for N-Myc-regulated transcriptional activation and tumorigenesis Using ChIP-Seq, We profiled key epigenetic marks H3K4 trimethylation in BE(2)-C neuroblastoma cells transfected with control siRNA or WDR5 siRNA-1 at N-Myc target gene promoters The results showed knockdown WDR5 significantly reduced H3K4me3 at 93.2% of N-Myc binding promoters, but only at 53.5% of N-Myc non-binding promoters. Identification of Histone H3K4 trimethylation and N-Myc binding sites in BE(2)-C cells transfected with control siRNA or WDR5 siRNA-1.

ORGANISM(S): Homo sapiens

SUBMITTER: Tao Liu

PROVIDER: E-GEOD-70098 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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The histone H3 lysine 4 presenter WDR5 induces N-Myc target gene transcription and promotes neuroblastoma [ChIP-Seq]

Project description:WDR5 is an important co-factor for N-Myc-regulated transcriptional activation and tumorigenesis Using ChIP-Seq, We profiled key epigenetic marks H3K4 trimethylation in BE(2)-C neuroblastoma cells transfected with control siRNA or WDR5 siRNA-1 at N-Myc target gene promoters The results showed knockdown WDR5 significantly reduced H3K4me3 at 93.2% of N-Myc binding promoters, but only at 53.5% of N-Myc non-binding promoters.

2015-12-31 | GSE70098 | GEO

The histone H3 lysine 4 presenter WDR5 induces N-Myc target gene transcription and promotes neuroblastoma [gene expression]

Project description:WDR5 is an important co-factor for N-Myc-regulated transcriptional activation and tumorigenesis We analysed whether WDR5 siRNAs modulate gene expression Neuroblastoma BE(2)-C cells were treated with control siRNA, WDR5 siRNA-1, and WDR5 siRNA-2 for 40 hours, and subjected to differential gene expression studies with Affymetrix microarrays.

2015-12-31 | E-GEOD-69861 | biostudies-arrayexpress

Essential role of lncRNA binding for WDR5 maintenance of active chromatin and embryonic stem cell pluripotency

Project description:Here we delineate the roles of RNA binding for WDR5 function on chromatin state and murine embryonic stem cell (ESC) maintenance. Examination of global transcriptional changes and mapping genome-wide transcription factors occupancy at distinct time points during the transdifferentiation process

2014-02-12 | E-GEOD-53035 | biostudies-arrayexpress

Altered expression of genes in WDR5 knockdown

Project description:WDR5 (WD repeat domain 5) plays an important role in the epigenetic regulation of gene transcription, involing in regulation of embryonic stem cell and cancer cell.Bladder cancer is one of the most common cancers that cause approximately 150,000 deaths per year worldwide.The goal of this study is to identify the target genes of WDR5 in bladder cancer.Our results inditcate that the genes regulated by WDR5 involved in a variety of biological functions, such as proliferation and anti-apoptosis. Bladder cancer cell line UM-UC-3 was transfected with the contol siRNA or two different WDR5 siRNA for 48h. The RNA of the transfected cells was extracted and hybridized on Affymetrix microarrays. We indentified the putative target genes of WDR5 in both WDR5 siRNA by comparing the diferent expressed genes among control, si-WDR5-2 and si-WDR5-3. We futher validated the data of microarray in UM-UC-3 and T24 by RT-qPCR and Western bloting.

2015-02-09 | E-GEOD-59132 | biostudies-arrayexpress

A Role for WDR5 in Integrating Threonine 11 Phosphorylation to Lysine 4 Methylationon Histone H3 and in Prostate Cancer

Project description:Upon androgen stimulation, PKN1-mediated histone H3 threonine 11 phosphorylation (H3T11P) promotes AR target genes activation. However, the underlying mechanism is not completely understood. Here, we show that WDR5, a subunit of the SET1/MLL complex, interacts with H3T11P and this interaction facilitates the recruitment of the SET1/MLL complex and subsequent H3K4 trimethylation (H3K4me3). Using ChIP-seq, we find that androgen stimulation results in a six-fold increase in the number of H3T11P-marked regions and induces WDR5 colocalization to one third of H3T11P-enriched promoters, thus establishing a genome-wide relationship between H3T11P and recruitment of WDR5. Accordingly, PKN1 knock-down or chemical inhibition severely blocks WDR5 association and H3K4me3 on AR target genes. Finally, WDR5 is critical in prostate cancer cell proliferation, and is hyperexpressed in human prostate cancers. Together, these results identify WDR5 as a critical epigenomic integrator of histone phosphorylation and methylation and a major driver of androgen-dependent prostate cancer cell proliferation. Identification of Histone 3 threonine 11 phosphorylation (H3T11P) marks and WDR5 binding sites in LNCaP cells treated with R1881 ligand (androgen) or solvent control.

2014-07-01 | E-GEOD-55279 | biostudies-arrayexpress

WDR5 protein interactions at the WIN-site

Project description:The WIN site of WDR5 is a druggable pocket that impairs WDR5 protein function and carries therapeutic potential for treating cancer. This study evaluates the protein interactions affected by small molecule blockade of this surface on WDR5. Inhibited and uninhibited WDR5-containing complexes from HEK293 cells were quantitatively compared by SILAC-based proteomics. Of the high confidence proteins affected by this inhibition, one protein, PDPK1, was investigated further by mass spectrometry for identification of post translational modifications that could influence binding to WDR5.

2021-01-25 | PXD019209 | Pride

Long noncoding RNA as regulatory switch of protein turnover

Project description:Long intervening noncoding RNAs (lincRNAs) are prevalent genes with poorly understood functions. Here we discover a pathway of lincRNA-regulated proteolysis. The enhancer-like lincRNA HOTTIP extends the half-life of its binding protein WDR5, a subunit of the MLL H3K4 methylase complex, resulting in increased chromatin occupancy and gene activation. LincRNA-mediated stabilization requires direct RNA-protein interaction in a long RNA context, and blocks turnover at a step after target protein poly-ubiquitination. We elucidate the lincRNA binding interface on WDR5. A WDR5 mutant that selectively abrogates lincRNA binding becomes unstable, and is defective in gene activation, maintenance of histone H3 lysine 4 trimethylation, and embryonic stem cell self renewal. The ability to modulate protein turnover may allow lincRNAs to control the lifespan of molecular interactions at chromatin and elsewhere, broadening their scope in epigenetics and cell fate control. Gene expression analysis: To establish a differentiation signature for mouse V6.5 ES cells infected with anti mouse WDR5 shRNA, rescued with doxycycline inducible WDR5 WT or WDR5 F266A, total RNA was isolated in biologic duplicate from cells in different conditions and hybridized to Affymetrix Mouse 430 2.0 arrays.

2013-02-18 | E-GEOD-36513 | biostudies-arrayexpress

Genome-wide binding of WDR5 and GRHL3

Project description:The antagonistic actions of Polycomb and Trithorax are responsible for proper cell fate determination in mammalian tissues. In the epidermis, a self-renewing epithelium, previous work has shown that release from Polycomb repression only partially explains differentiation gene activation. We now show that Trithorax is also a key regulator of epidermal differentiation, not only through activation of genes repressed by Polycomb in progenitor cells, but also through activation of genes independent of regulation by Polycomb. The differentiation associated transcription factor GRHL3/GET1 recruits the ubiquitously expressed Trithorax complex to a subset of differentiation genes. Examination of WDR5 and GRHL3 binding in human differentited primary keratinocytes (NHEK). High calcium medium was added to NHEK cells at 50% confluency to induce differentiation. Cells were collected for ChIP 24 hours after addition of high calcium medium. ChIP with Wdr5 and Grhl3 antibodies, and an input control were sequenced.

2012-11-10 | E-GEOD-42180 | biostudies-arrayexpress

Differential gene expression in neuroblastoma cells after transfection with control siRNA, N-Myc siRNA-1, N-Myc siRNA-2, lncMycN siRNA-1 or lncMycN siRNA-2

Project description:N-Myc oncoprotein induces neuroblastoma by modulating gene transcription, and long noncoding RNAs exert biological effects by regulating gene expression. We analysed whether N-Myc and the long noncoding RNA lncMycN mediate the expression of common subsets of genes. Neuroblastoma Kelly cells were transfected with control siRNA, N-Myc siRNA-1, N-Myc siRNA-2, lncMycN siRNA-1 or lncMycN siRNA-2. RNA was extracted from the cells 48 hours after siRNA transfections, and subjected to differential gene expression studies with Affymetrix microarrays.

2015-03-31 | E-GEOD-50959 | biostudies-arrayexpress

Characterization of Spp1-TAP and Mer2-TAP interactomes

Project description:Histone H3K4 methylation is a feature of meiotic recombination hotspots shared by many organisms including plants and mammals. Meiotic recombination is initiated by programmed double strand break (DSB) formation that in budding yeast is directed in gene promoters by histone H3K4 di/trimethylation. This histone modification is indeed recognized by Spp1, a PHD-finger containing protein that belongs to the conserved histone H3K4 methyltransferase Set1 complex. During meiosis, Spp1 binds H3K4me and recruits a DSB protein, Mer2, to promote DSB formation close to gene promoters. How Set1C and Mer2 related functions of Spp1 are connected is not clear.

2018-01-30 | PXD007590 | Pride

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