Jul 21, 2016

SMARCA4 regulates gene expression and higher-order chromatin structure in proliferating mammary epithelial cells

Genome Research
A Rasim BarutcuAnthony N Imbalzano

Abstract

The packaging of DNA into chromatin plays an important role in transcriptional regulation and nuclear processes. Brahma-related gene-1 SMARCA4 (also known as BRG1), the essential ATPase subunit of the mammalian SWI/SNF chromatin remodeling complex, uses the energy from ATP hydrolysis to disrupt nucleosomes at target regions. Although the transcriptional role of SMARCA4 at gene promoters is well-studied, less is known about its role in higher-order genome organization. SMARCA4 knockdown in human mammary epithelial MCF-10A cells resulted in 176 up-regulated genes, including many related to lipid and calcium metabolism, and 1292 down-regulated genes, some of which encode extracellular matrix (ECM) components that can exert mechanical forces and affect nuclear structure. ChIP-seq analysis of SMARCA4 localization and SMARCA4-bound super-enhancers demonstrated extensive binding at intergenic regions. Furthermore, Hi-C analysis showed extensive SMARCA4-mediated alterations in higher-order genome organization at multiple resolutions. First, SMARCA4 knockdown resulted in clustering of intra- and inter-subtelomeric regions, demonstrating a novel role for SMARCA4 in telomere organization. SMARCA4 binding was enriched at topologically asso...Continue Reading

Mentioned in this Paper

Establishment and Maintenance of Localization
BRAHMA
Transcriptional Regulation
Nucleosomes
ATP5B protein, human
Exertion
Gene Knockdown Techniques
Genome
Genes
Extracellular Matrix Constituent Secretion

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