Identifying Nuclear Matrix-Attached DNA Across the Genome

Jason R. Dobson, Deli Hong, A. Rasim Barutcu, Hai Wu, Anthony N. Imbalzano, Jane B. Lian, Janet L. Stein, Andre J van Wijnen, Jeffrey A. Nickerson, Gary S. Stein

Research output: Contribution to journalArticle

11 Scopus citations

Abstract

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.

Original languageEnglish (US)
JournalJournal of Cellular Physiology
DOIs
StateAccepted/In press - 2016

ASJC Scopus subject areas

  • Medicine(all)
  • Physiology
  • Clinical Biochemistry
  • Cell Biology

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    Dobson, J. R., Hong, D., Barutcu, A. R., Wu, H., Imbalzano, A. N., Lian, J. B., Stein, J. L., van Wijnen, A. J., Nickerson, J. A., & Stein, G. S. (Accepted/In press). Identifying Nuclear Matrix-Attached DNA Across the Genome. Journal of Cellular Physiology. https://doi.org/10.1002/jcp.25596