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WIN 18,446 2dpp testis culture

ABSTRACT: Analysis of 2dpp whole testes cultured for 24h in the presence of WIN 18,446, a BDAD compound. BDADs (Bis-(dichloroacetyl)-diamines) have been shown previously to inhibit spermatogenesis and function as male contraceptives in many species; however, their mechanism of action has yet to be fully described. Results provide insight into the ability of WIN 18,446 to inhibit retinoic acid synthesis in the murine testis.

ORGANISM(S): Mus musculus

PROVIDER: GSE25610 | GEO | 2010/11/25

SECONDARY ACCESSION(S): PRJNA134261

REPOSITORIES: GEO

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WIN 18,446 2dpp testis culture

Project description:Analysis of 2dpp whole testes cultured for 24h in the presence of WIN 18,446, a BDAD compound. BDADs (Bis-(dichloroacetyl)-diamines) have been shown previously to inhibit spermatogenesis and function as male contraceptives in many species; however, their mechanism of action has yet to be fully described. Results provide insight into the ability of WIN 18,446 to inhibit retinoic acid synthesis in the murine testis. Testes were removed from 2dpp 129 mice and cultured for 24h in an organ culture mold in the presence of WIN 18,446. Total RNA was extracted and hybridized to Affymetrix Mouse Genome 430 2.0 arrays.

2010-11-25 | E-GEOD-25610 | biostudies-arrayexpress

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Project description:WIN Site inhibitors bind the WIN Site of WDR5 resulting in decreased transcription of WDR5 target genes, many of which encode components of the protein synthesis machinery. In this study, we determined proteome alterations in an MLL-rearranged leukemia cell line treated for either 24 or 72 hours with a WIN Site inhibitor. The data from these studies, along with Ribo-Seq, RNA-Seq, and CRISPR screen experiments, guided us in assembling a collection of compounds that, when combined with WIN Site inhibitor, synergistically inhibit growth of MLL-rearranged leukemia cells.

2023-07-04 | PXD035129 | Pride

Multiomic characterization of WDR5 WIN site inhibition reveals actionable synergies for MLL-rearranged leukemia

Project description:In this study, we utilized a multi-omics approach to determine the transcriptional, translational, and proteomic responses to WIN Site inhibition in MLL-rearranged leukemia cells via RNA-Seq, Ribo-Seq, and quantitative proteomics, respectively. We also performed both a whole-genome targeting primary CRISPR screen and a secondary CRISPR screen targeting a currated collection of genes to determine genes important for sensitivity to WIN Site inhibition. These combined data sets rationally guided us in assembling a collection of compounds that, when combined with WIN Site inhibitor, synergistically inhibit growth of MLL-rearranged leukemia cells.

2023-07-03 | GSE206931 | GEO

Adult mouse stage synchronized testis array

Project description:WIN 18,446/RA treatment of neonatal male mice was used to synchronize spermatogenesis to 2-3 different stages of the cycle of the seminiferous epithelium in the adult testis

2014-12-17 | GSE64214 | GEO

The WDR5 WIN site interactome

Project description:The WIN site of WDR5 is a druggable pocket that is crucial for WDR5 protein function and carries therapeutic potential for treating cancer. This study evaluates the protein interactions affected by small molecule blockade of the WIN site of WDR5. We find that PDPK1 directly binds the WIN site of WDR5, and we investigate this newfound interaction through proteomic, biochemical, and genomic methods.

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Adult mouse stage synchronized testis array

Project description:WIN 18,446/RA treatment of neonatal male mice was used to synchronize spermatogenesis to 2-3 different stages of the cycle of the seminiferous epithelium in the adult testis 6 different groups of synchronized adult mouse testis samples (N = 2 per group), each representing only 2-3 stages of the cycle, were collected and analyzed using GeneChip Mouse Gene ST 1.0 Arrays

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The WDR5 WIN site interactome

Project description:The WDR5 WIN site interactome

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Project description:The aim of this project was to explore the role of muscarinic receptors (M1, M3, and M5) in spermatogenesis. The lentivirus with the knockdown of M1, M3, M5 were injected into mouse testes. Then the testes were collected. The RNA was used for the RNA-seq analysis to search the role of these receptors in the spermatogenesis.

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WIN site inhibition disrupts a subset of WDR5 function

Project description:This study demonstrates the impact of WIN site inhibitors versus WDR5 degradation on H3K4me and transcriptional processes in human Burkitt's lymphoma cells. We use RNA-seq to measure global transcript levels, ChIP-seq to map genomic H3K4me3, and PRO-seq to map genomic polymerase density and primary transcripts. Our data show that WIN site inhibition disables only a specific subset of WDR5 activity, and that H3K4me changes induced by WDR5 depletion do not explain accompanying transcriptional responses.

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comparison of MILI+/- and MILI-/- at D10 testis

Project description:Spermatogenesis in MILI-KO mice was blocked completely at early prophase of the first meiosis during the zygotene and early pachytene stage. To analyze the molecular basis of MILI function, we examined the difference between gene expression for MILI-/- and MILI+/- testes. Keywords: total RNAs of day10 testes

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