Multi-component epigenetic control of pro-invasive genes in cancer cells (ChIP-chip)

ABSTRACT: To identify the epigenetic signature that controls cancer cell migration, we performed integrated gene expression, miRNA and epigenetic profiling of 486 selected invasion-associated genes in non-migratory MCF-7 breast carcinoma and highly migratory U251 glioma cells. We used a custom-built chromatin immunoprecipitation (ChIP)-on-Chip microarray that included complimentary oligonucleotide probes for the genes that were functionally linked to proteolysis, migration and tumorigenesis such as extracellular matrix proteins, cellular proteinases and their inhibitors, growth factors and cytokines, and adhesion and signaling receptors. As a result, we determined the role histone H3 modifications [(Lys-4 dimethylation (H3K4me2), Lys-27 trimethylation (H3K27me3) and acetylation (H3ac)] play in transcriptional regulation of the multiple invasion-associated genes. Predominantly, transcriptional silencing of the pro-invasive genes in MCF-7 cells involved the repressive H3K27me3 mark and, frequently, the presence of the stem cell-like bivalent epigenetic mark (enrichment in both H3K27me3 and H3K4me2). In turn, pro-invasive genes in U251 cells were epigenetically stimulated by a gain in H3K4me2 and histone H3 hyperacetylation, and by a global reduction of H3K27me3. Intriguingly, the expression of multiple collagen genes was highly enhanced in glioma cells, thus suggesting that gliomas themselves deposit a specialized, invasion-promoting matrix. Microarray probes were designed using eArray software (Agilent). Unique DNA probes specific to 486 human genes from the high density (HD) ChIP Database (Agilent) were included in each microarray. Microarray, 8x15K format, slides were custom manufactured by Agilent. Additional hybridization control probes (universal control grid LA577) were included in the arrays (Agilent). Each individual probe in the microarray was replicated 3-10 times. MCF7 vs.U251 cells

ORGANISM(S): Homo sapiens

SUBMITTER: Andrei Chernov 

PROVIDER: E-GEOD-18890 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress