Identifying Nuclear Matrix-Attached DNA Across the Genome
Department of Cell and Developmental Biology; UMass Metabolic Network
Cell Biology | Cellular and Molecular Physiology | Computational Biology | Genomics | Molecular Genetics
Experimental approaches to define the relationship between gene expression and nuclear matrix attachment regions (MARs) have given contrasting and method-specific results. We have developed a next generation sequencing strategy to identify MARs across the human genome (MAR-Seq). The method is based on crosslinking chromatin to its nuclear matrix attachment sites to minimize changes during biochemical processing. We used this method to compare nuclear matrix organization in MCF-10A mammary epithelial-like cells and MDA-MB-231 breast cancer cells and evaluated the results in the context of global gene expression (array analysis) and positional enrichment of gene-regulatory histone modifications (ChIP-Seq). In the normal-like cells, nuclear matrix-attached DNA was enriched in expressed genes, while in the breast cancer cells, it was enriched in non-expressed genes. In both cell lines, the chromatin modifications that mark transcriptional activation or repression were appropriately associated with gene expression. Using this new MAR-Seq approach, we provide the first genome-wide characterization of nuclear matrix attachment in mammalian cells and reveal that the nuclear matrix-associated genome is highly cell-context dependent.
DOI of Published Version
J Cell Physiol. 2016 Sep 14. doi: 10.1002/jcp.25596. Link to article on publisher's site
Journal of cellular physiology
Dobson, Jason; Hong, Deli; Barutcu, Rasim; Wu, Hai; Imbalzano, Anthony N.; Lian, Jane B.; Stein, Janet L.; Van Wijnen, Andre J.; Nickerson, Jeffrey A.; and Stein, Gary S., "Identifying Nuclear Matrix-Attached DNA Across the Genome" (2016). University of Massachusetts Medical School Faculty Publications. 1051.