Transcriptomics

Dataset Information

0

Expression and ChIP-chip data from REH and SEM leukemia cell lines


ABSTRACT: MLL-fusion proteins are potent inducers of cancer in hematopoietic cells, where they are known to cause changes in global gene expression. How MLL-fusion proteins interact with the genome has not been established, so we have limited understanding of the pathway by which these proteins generate aberrant gene expression programs. Here we describe how the MLL-AF4 protein occupies the genome in human leukemia cells and its striking effects on chromatin states. We find that the MLL-AF4 fusion protein selectively occupies regions of the genome that contain developmental regulatory genes important for hematopoietic stem cell identity and self-renewal. These MLL-AF4 bound regions have grossly altered chromatin structure, with histone modifications catalyzed by Trithorax Group (TrxG) proteins and Dot1 extending across unusually large domains. This indicates that a key feature of MLL-associated leukemogenesis is aberrant targeting of chromatin modifiers to regions of the genome controlling hematopoietic development. Our results define the direct targets of the MLL-fusion protein, reveal the global role of epigenetic misregulation in leukemia, and identify new targets for therapeutic intervention in human cancer. Keywords: cell type comparison This dataset includes expression data for two replicates each of SEM and REH leukemia cell lines and ChIP-chip data targeting RNAP2, H3K4me3, H3K79me2, ENL, AF4-C, and MLL-N in SEM and REH leukemia cell lines.

ORGANISM(S): Homo sapiens  

SUBMITTER: Garrett M Frampton  

PROVIDER: E-GEOD-13313 | ArrayExpress | 2008-12-14

SECONDARY ACCESSION(S): GSE13313PRJNA109897

REPOSITORIES: GEO, ArrayExpress

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Publications

Aberrant chromatin at genes encoding stem cell regulators in human mixed-lineage leukemia.

Guenther Matthew G MG   Lawton Lee N LN   Rozovskaia Tatiana T   Frampton Garrett M GM   Levine Stuart S SS   Volkert Thomas L TL   Croce Carlo M CM   Nakamura Tatsuya T   Canaani Eli E   Young Richard A RA  

Genes & development 20081201 24


Mixed-lineage leukemia (MLL) fusion proteins are potent inducers of leukemia, but how these proteins generate aberrant gene expression programs is poorly understood. Here we show that the MLL-AF4 fusion protein occupies developmental regulatory genes important for hematopoietic stem cell identity and self-renewal in human leukemia cells. These MLL-AF4-bound regions have grossly altered chromatin structure, with histone modifications catalyzed by trithorax group proteins and DOT1 extending across  ...[more]

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