title: An integrative genomic and epigenomic approach for the study of transcriptional regulation.
abstract: 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.
authors: Department of Developmental and Molecular Biology, Albert Einstein College of Medicine, Bronx, New York, United States of America.
authors: Maria E
authors: ME
authors: Figueroa
authors: Mark
authors: M
authors: Reimers
authors: Reid F
authors: RF
authors: Thompson
authors: Kenny
authors: K
authors: Ye
authors: Yushan
authors: Y
authors: Li
authors: Rebecca R
authors: RR
authors: Selzer
authors: Jakob
authors: J
authors: Fridriksson
authors: Elisabeth
authors: E
authors: Paietta
authors: Peter
authors: P
authors: Wiernik
authors: Roland D
authors: RD
authors: Green
authors: John M
authors: JM
authors: Greally
authors: Ari
authors: A
authors: Melnick
mesh_terms: D000107:Acetylation; D001483:Base Sequence; D045744:Cell Line, Tumor; D047369:Chromatin Immunoprecipitation; D019175:DNA Methylation; D017931:DNA Primers; D005786:Gene Expression Regulation; D023281:Genomics; D006657:Histones / Q000378:metabolism; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000235:genetics / Q000473:pathology; D020411:Oligonucleotide Array Sequence Analysis; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics / Q000473:pathology; D014158:Transcription, Genetic
chemical_list: D017931:DNA Primers; D006657:Histones