Epigenetic regulation of tumor progression and metastasis by chromatin remodeling factor SATB1

Abstract

Special AT-rich sequence binding protein 1 (SATB1) is a nuclear protein that functions as a global chromatin organizer, regulating chromatin structure and gene expression. Recently, it has been reported that SATB1 is highly expressed in metastatic breast cancer cells and promotes growth and metastasis by reprogramming transcription profiles, suggesting SATB1 as a potential prognostic marker and therapeutic target for metastatic breast cancer. Although SATB1 is known to regulate hundreds of genes, it’s binding to endogenous genes and regulation mechanism have rarely been demonstrated. In this study, we performed a systematic, genome-wide analysis of the functional significance of SATB1 in breast cancer cells. With the use of chromatin immunoprecipitation coupled with next-generation sequencing (ChIP-seq), we identified around 20,000 SATB1-binding genomic regions. Also, we established epigenomic profiles for metastatic breast cancer cells using SATB1 loss-of-function system, and explored the role of SATB1 in the change of chromatin structure which is associated with gene expression. This comprehensive analysis of multiple epigenome data provides several novel SATB1-target genes which regulate growth and metastasis of breast cancer cells