An integrative genomic and epigenomic approach for the study of transcriptional regulation

Maria E. Figueroa, Mark Reimers, Reid Thompson, Kenny Ye, Yushan Li, Rebecca R. Selzer, Jakob Fridriksson, Elisabeth Paietta, Peter Wiernik, Roland D. Green, John M. Greally, Ari Melnick

Research output: Contribution to journalArticle

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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.

Original languageEnglish (US)
Article numbere1882
JournalPloS one
Volume3
Issue number3
DOIs
StatePublished - Mar 26 2008
Externally publishedYes

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leukemia
Epigenomics
Gene expression
epigenetics
myeloid leukemia
lymphocytic leukemia
Leukemia
acetylation
Acetylation
Precursor Cell Lymphoblastic Leukemia-Lymphoma
genomics
Gene Expression
Acute Myeloid Leukemia
gene expression
neoplasms
Microarrays
Tumors
Neoplasms
Genes
cytosine

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Figueroa, M. E., Reimers, M., Thompson, R., Ye, K., Li, Y., Selzer, R. R., ... Melnick, A. (2008). An integrative genomic and epigenomic approach for the study of transcriptional regulation. PloS one, 3(3), [e1882]. https://doi.org/10.1371/journal.pone.0001882

An integrative genomic and epigenomic approach for the study of transcriptional regulation. / Figueroa, Maria E.; Reimers, Mark; Thompson, Reid; Ye, Kenny; Li, Yushan; Selzer, Rebecca R.; Fridriksson, Jakob; Paietta, Elisabeth; Wiernik, Peter; Green, Roland D.; Greally, John M.; Melnick, Ari.

In: PloS one, Vol. 3, No. 3, e1882, 26.03.2008.

Research output: Contribution to journalArticle

Figueroa, ME, Reimers, M, Thompson, R, Ye, K, Li, Y, Selzer, RR, Fridriksson, J, Paietta, E, Wiernik, P, Green, RD, Greally, JM & Melnick, A 2008, 'An integrative genomic and epigenomic approach for the study of transcriptional regulation', PloS one, vol. 3, no. 3, e1882. https://doi.org/10.1371/journal.pone.0001882
Figueroa, Maria E. ; Reimers, Mark ; Thompson, Reid ; Ye, Kenny ; Li, Yushan ; Selzer, Rebecca R. ; Fridriksson, Jakob ; Paietta, Elisabeth ; Wiernik, Peter ; Green, Roland D. ; Greally, John M. ; Melnick, Ari. / An integrative genomic and epigenomic approach for the study of transcriptional regulation. In: PloS one. 2008 ; Vol. 3, No. 3.
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