TitleAn integrative genomic and epigenomic approach for the study of transcriptional regulation.
Publication TypeJournal Article
Year of Publication2008
AuthorsFigueroa, Maria E., Reimers Mark, Thompson Reid F., Ye Kenny, Li Yushan, Selzer Rebecca R., Fridriksson Jakob, Paietta Elisabeth, Wiernik Peter, Green Roland D., Greally John M., and Melnick Ari
JournalPLoS One
Date Published2008 Mar 26
KeywordsAcetylation, Base Sequence, Cell Line, Tumor, Chromatin Immunoprecipitation, DNA Methylation, DNA Primers, Gene Expression Regulation, Genomics, Histones, Humans, Leukemia, Myeloid, Acute, Oligonucleotide Array Sequence Analysis, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Transcription, Genetic

<p>The molecular heterogeneity of acute leukemias and other tumors constitutes a major obstacle towards understanding disease pathogenesis and developing new targeted-therapies. Aberrant gene regulation is a hallmark of cancer and plays a central role in determining tumor phenotype. We predicted that integration of different genome-wide epigenetic regulatory marks along with gene expression levels would provide greater power in capturing biological differences between leukemia subtypes. Gene expression, cytosine methylation and histone H3 lysine 9 (H3K9) acetylation were measured using high-density oligonucleotide microarrays in primary human acute myeloid leukemia (AML) and acute lymphocytic leukemia (ALL) specimens. We found that DNA methylation and H3K9 acetylation distinguished these leukemias of distinct cell lineage, as expected, but that an integrative analysis combining the information from each platform revealed hundreds of additional differentially expressed genes that were missed by gene expression arrays alone. This integrated analysis also enhanced the detection and statistical significance of biological pathways dysregulated in AML and ALL. Integrative epigenomic studies are thus feasible using clinical samples and provide superior detection of aberrant transcriptional programming than single-platform microarray studies.</p>

Alternate JournalPLoS One
PubMed ID18365023
PubMed Central IDPMC2266992
Grant ListR01 CA104348 / CA / NCI NIH HHS / United States
R01 HD044078 / HD / NICHD NIH HHS / United States
T32 GM007288 / GM / NIGMS NIH HHS / United States
GM007288 / GM / NIGMS NIH HHS / United States