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Identifying Nuclear Matrix‐Attached DNA Across the Genome
Author(s) -
Dobson Jason R.,
Hong Deli,
Barutcu A. Rasim,
Wu Hai,
Imbalzano Anthony N.,
Lian Jane B.,
Stein Janet L.,
van Wijnen Andre J.,
Nickerson Jeffrey A.,
Stein Gary S.
Publication year - 2017
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.25596
Subject(s) - nuclear matrix , scaffold/matrix attachment region , chromatin , biology , gene , genome , gene expression , context (archaeology) , histone , computational biology , dna , microbiology and biotechnology , genetics , chromatin remodeling , paleontology
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. J. Cell. Physiol. 232: 1295–1305, 2017. © 2016 Wiley Periodicals, Inc.