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Series GSE247777 Query DataSets for GSE247777
Status Public on Nov 19, 2023
Title The Hippo kinase LATS1 controls CTCF chromatin occupancy and the hormonal response of three-dimensionally grown breast cancer cells
Organism Homo sapiens
Experiment type Expression profiling by high throughput sequencing
Other
Genome binding/occupancy profiling by high throughput sequencing
Summary The cancer epigenome has been studied in cells cultured in 2D monolayers on plastic surfaces, but recent studies highlight the impact of the extracellular matrix (ECM) and the 3D environment on multiple cellular functions. Here, we report the physical, biochemical and genomic differences between T47D breast cancer cells cultured in 2D monolayer and as 3D spheroids in Matrigel. Cells within 3D spheroids exhibit a rounder nucleus with less accessible, more compacted chromatin, and altered expression of over 2,000 genes, the majority of which become repressed. Hi-C analysis reveals that cells grown in 3D exhibit enrichment in regions belonging to the B compartment, decrease on chromatin bound CTCF and increased fusion of Topologically Associating Domains (TADs). Upregulation of the Hippo pathway in 3D spheroids results in the activation of the LATS1 kinase, which promotes phosphorylation and displacement of CTCF from DNA, likely responsible for the observed TAD fusions. Cells grown in 3D exhibit higher progesterone receptor (PR) binding to chromatin, leading to an increase in the number hormone-regulated genes. This effect is in part mediated by the LATS1 activation, which favors cytoplasmic retention of YAP and CTCF removal.
 
Overall design Epigenomic analysis of LATS1 kinase in controlling CTCF for 3D growth of breast cancer cells
Web link https://www.embopress.org/doi/full/10.1038/s44318-024-00080-x
 
Contributor(s) Cuellar JR, Ferrari R, Sanz RT, Nach AS, Castillo D, Le Dily F, Neguembor MV, Malatesta M, Marti-Renom MA, Beato M, Vicent GP
Citation(s) 38565950
Submission date Nov 14, 2023
Last update date Apr 03, 2024
Contact name Roberto Ferrari
E-mail(s) roberto.ferrari1@unipr.it
Phone 0521905646
Organization name University of Parma
Department Department of Chemistry, Life Sciences and Environmental Sustainability
Lab Molecular Cell Biology of the Epigenome (MCBE)
Street address Parco Area delle Scienze 23/A
City Parma
State/province Parma
ZIP/Postal code 43124
Country Italy
 
Platforms (1)
GPL16791 Illumina HiSeq 2500 (Homo sapiens)
Samples (73)
GSM7900628 ChIP-seq of CTCF at T0 in 2D culture
GSM7900629 ChIP-seq of CTCF at T30 in 2D culture
GSM7900630 ChIP-seq of H3K27ac at T0 in 2D culture
Relations
BioProject PRJNA1040302

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE247777_RAW.tar 27.4 Gb (http)(custom) TAR (of BIGWIG, BW, HIC)
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Raw data are available in SRA

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