Specific chromatin landscapes and transcription factors couple breast cancer subtype with metastatic relapse to lung or brain.

BMC Medical Genomics
Wesley L CaiDon X Nguyen

Abstract

Few somatic mutations have been linked to breast cancer metastasis, whereas transcriptomic differences among primary tumors correlate with incidence of metastasis, especially to the lungs and brain. However, the epigenomic alterations and transcription factors (TFs) which underlie these alterations remain unclear. To identify these, we performed RNA-seq, Chromatin Immunoprecipitation and sequencing (ChIP-seq) and Assay for Transposase-Accessible Chromatin using sequencing (ATAC-seq) of the MDA-MB-231 cell line and its brain (BrM2) and lung (LM2) metastatic sub-populations. We incorporated ATAC-seq data from TCGA to assess metastatic open chromatin signatures, and gene expression data from human metastatic datasets to nominate transcription factor biomarkers. Our integrated epigenomic analyses found that lung and brain metastatic cells exhibit both shared and distinctive signatures of active chromatin. Notably, metastatic sub-populations exhibit increased activation of both promoters and enhancers. We also integrated these data with chromosome conformation capture coupled with ChIP-seq (HiChIP) derived enhancer-promoter interactions to predict enhancer-controlled pathway alterations. We found that enhancer changes are associated...Continue Reading

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Citations

Apr 6, 2021·Frontiers in Genetics·Soledad OchoaEnrique Hernández-Lemus
Sep 15, 2021·The Biochemical Journal·Jocelyn F Chen, Qin Yan

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Methods Mentioned

BETA
Assay
HiChIP
RNA-seq
Immunoprecipitation
Hi-ChIP
ChIP-seq
deubiquitination

Software Mentioned

BioMart
edgeR
trimmomatic
PEPATAC
R script
MACS2
UpsetR
HiChIP
R package biomaRt
featureCounts

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