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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. Overall design: ChIP-seq of 3 histone modifications in 2 cell lines with 2 replicates</long_description><repository>ENA</repository></additional><is_claimable>false</is_claimable><name>Homo sapiens</name><description>Identifying Nuclear Matrix–attached DNA across the Genome (ChIP-seq)</description><dates><last_updated>2025-09-24</last_updated><first_public>2016-10-07</first_public></dates><accession>PRJNA345501</accession><cross_references><GEO>GSE87662</GEO><taxon>9606</taxon><PubMed>27627025</PubMed></cross_references></HashMap>