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WDR5 activity regulates nuclear changes and migration of acute lymphoblastic leukemia cells across confined spaces [Jurkat]

ABSTRACT: WDR5 activity regulates nuclear changes and migration of acute lymphoblastic leukemia cells across confined spaces [Jurkat]

PROVIDER: PRJNA796234 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR17548921.fastq.gz	Fastqsanger.gz
	SRR17548922.fastq.gz	Fastqsanger.gz
	SRR17548923.fastq.gz	Fastqsanger.gz
	SRR17548924.fastq.gz	Fastqsanger.gz
	SRR17548925.fastq.gz	Fastqsanger.gz

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WDR5 activity regulates nuclear changes and migration of acute lymphoblastic leukemia cells across confined spaces [Jurkat]

Project description:Purpose: Acute lymphoblastic leukemia (ALL) is the most common pediatric cancer and infiltration of leukemic cells is critical for disease progression and relapse. In spite of the canonical functions of epigenetics in transcription and DNA homeostasis, its contribution to the nuclear deformability of migrating leukemic cells remains unclear. The objective was to evaluate the role of WDR5 (a core subunit of the histone H3K4 methyltransferases) during leukemia cell migration. Experimental design: We used ALL cell lines and primary samples from patients to study their response and migration in 3D environments and how they extravasate in a mouse xenograft model. We also performed, biophysical, transcriptional and ChIP-sequencing analyses to determine the mechanism by which WDR5 controls ALL progression. Results: We observed that WDR5 activity is critical for ALL cell invasion into 3D collagen matrices. Notably, blocking WDR5 activity also decreased the extravasation of ALL cells in an in vivo model. We identified that 3D constrained conditions promoted H3K4 methylation in ALL cells that altered the global chromatin configuration and transcriptional changes related to cell cycle and DNA replication. WDR5 inhibition did not impair cell adhesion or cell response to chemokines; but we demonstrated that 3D conditions affected the deformation and biophysical behavior of the nucleus in ALL cells. Conclusions: We conclude that confined conditions have a fundamental role in ALL cell biology and provide novel molecular and biophysical mechanisms used by leukemia cells to disseminate. Targeting WDR5 might be a promising therapeutic strategy against ALL infiltration and dissemination.

2024-01-11 | GSE193440 | GEO

WDR5 activity regulates nuclear changes and migration of acute lymphoblastic leukemia cells across confined spaces.

2024-01-14 | GSE193383 | GEO

WDR5 activity regulates nuclear changes and migration of acute lymphoblastic leukemia cells across confined spaces.

Project description:WDR5 activity regulates nuclear changes and migration of acute lymphoblastic leukemia cells across confined spaces.

| PRJNA796000 | ENA

Wdr5

Project description:Wdr5

| PRJNA739648 | ENA

RNA sequencing to analyze trasncriptional profiles and screen potential regulators in confined migration

Project description:To identify potential regulators involved in confined cell migration, we performed transwell migration assay with 3 μm pore size to simulate native physical confined microenvironment. Transmigrated cells were collected for RNA sequencing to analyze transcriptional profile changes in comparison to parental cells.

2025-02-21 | GSE286976 | GEO

Confined Migration Induces Heterochromatin Formation and Alters Chromatin Accessibility

Project description:We show that confined migration results in predominantly decreased chromatin accessibility, consistent with the increased heterochromatin marks staining. A small fraction of ATAC-seq peaks shows increased accessibility at gene promoters of diverse pathways, such as chromatin silencing, tumor invasion, and DNA damage response; whereas the majority shows decreased accessibility at intergenic regions near centromeres or telomeres, suggesting possible heterochromatin spreading.

2022-08-10 | GSE181247 | GEO

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

Distinct signaling mechanisms regulate migration in unconfined versus confined spaces.

Project description:Using a microchannel assay, we demonstrate that cells adopt distinct signaling strategies to modulate cell migration in different physical microenvironments. We studied α4β1 integrin-mediated signaling, which regulates cell migration pertinent to embryonic development, leukocyte trafficking, and melanoma invasion. We show that α4β1 integrin promotes cell migration through both unconfined and confined spaces. However, unlike unconfined (2D) migration, which depends on enhanced Rac1 activity achieved by preventing α4/paxillin binding, confined migration requires myosin II-driven contractility, which is increased when Rac1 is inhibited by α4/paxillin binding. This Rac1-myosin II cross talk mechanism also controls migration of fibroblast-like cells lacking α4β1 integrin, in which Rac1 and myosin II modulate unconfined and confined migration, respectively. We further demonstrate the distinct roles of myosin II isoforms, MIIA and MIIB, which are primarily required for confined and unconfined migration, respectively. This work provides a paradigm for the plasticity of cells migrating through different physical microenvironments.

| S-EPMC3760608 | biostudies-literature

Confined Migration Induces Heterochromatin Formation and Alters Chromatin Accessibility

Project description:Confined Migration Induces Heterochromatin Formation and Alters Chromatin Accessibility

| PRJNA751211 | ENA

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

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