Unknown,Transcriptomics,Genomics,Proteomics

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Nitric oxide regulates gene expression in cancers by controlling histone posttranslational modifications [HiSeq 2000]

ABSTRACT: Dynamic changes in histone posttranslational modifications (PTMs) are important regulators of chromatin structure and gene transcription in both normal and disease settings. Herein, we describe a novel signaling mechanism of nitric oxide (â¢NO) by demonstrating its ability to modulate gene expression via alteration of histone PTMs. Having established that â¢NO exposure induced differential expression of approximately 6500 genes, we set out to determine if there was an epigenetic component to their regulation. â¢NO exposure led to alterations in the global levels of acetyl and methyl modifications at numerous lysine residues on core histones H3 and H4. Residues H3K9me2/ac were examined further and determined to have differential distribution at various loci throughout the genome in response to â¢NO. Changes in the enrichment levels of H3K9me2/ac at specific genes correlated with changes in the expression levels of their transcripts. Molecular mechanisms contributing to phenotypic outcomes in â¢NO-associated cancers remain to be well understood since traditional modes of â¢NO-signaling do not explain a large proportion of its impact on tumor cell behavior. Our results reveal that â¢NO drives a significant amount of gene expression changes epigenetically by changing the distribution of numerous histone marks. Cultured cells were treated with 500uM DETA/NO to examine the effects of a physiologically relevant â¢NO concentration on differential distribution of H3K9ac/H3K9me2. A total of two untreated biological replicates and two â¢NO-treated biological replicates were harvested. The untreated samples served as control against which comparisons were made to elucidate â¢NO-mediated changes in the histone landscape.

ORGANISM(S): Homo sapiens

SUBMITTER: Douglas Thomas

PROVIDER: E-GEOD-66318 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Nitric Oxide Regulates Gene Expression in Cancers by Controlling Histone Posttranslational Modifications.

Vasudevan Divya D Hickok Jason R JR Bovee Rhea C RC Pham Vy V Mantell Lin L LL Bahroos Neil N Kanabar Pinal P Cao Xing-Jun XJ Maienschein-Cline Mark M Garcia Benjamin A BA Thomas Douglas D DD

Cancer research 20151105 24

Altered nitric oxide (•NO) metabolism underlies cancer pathology, but mechanisms explaining many •NO-associated phenotypes remain unclear. We have found that cellular exposure to •NO changes histone posttranslational modifications (PTM) by directly inhibiting the catalytic activity of JmjC-domain containing histone demethylases. Herein, we describe how •NO exposure links modulation of histone PTMs to gene expression changes that promote oncogenesis. Through high-resolution mass spectrometry, we ...[more]

PMID: 26542213

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Dataset Information

Nitric oxide regulates gene expression in cancers by controlling histone posttranslational modifications [HiSeq 2000]

Publications

Nitric Oxide Regulates Gene Expression in Cancers by Controlling Histone Posttranslational Modifications.

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