Abstract
Histone lysine methylation and demethylation are considered critical steps in transcriptional regulation. In this report, we performed chromatin immunoprecipitation with microarray technology (ChIP-chip) analysis to examine the genome-wide occupancy of H3K9-me2 during all-trans-retinoic acid (ATRA)-induced differentiation of HL-60 promyelocytic leukemia cells. Using this approach, we found that KDM3B, which contains a JmjC domain, was downregulated during differentiation through the recruitment of a corepressor complex. Furthermore, KDM3B displayed histone H3K9-me1/2 demethylase activity and induced leukemogenic oncogene lmo2 expression via a synergistic interaction with CBP. Here, we found that KDM3B repressed leukemia cell differentiation and was upregulated in blood cells from acute lymphoblastic leukemia (ALL)-type leukemia patients. The combined results of this study provide evidence that the H3K9-me1/2 demethylase KDM3B might play a role in leukemogenesis via activation of lmo2 through interdependent actions with the histone acetyltransferase (HAT) complex containing CBP.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adaptor Proteins, Signal Transducing / genetics*
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Base Sequence
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Cell Differentiation / drug effects
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DNA, Neoplasm / genetics
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Gene Expression Regulation, Leukemic
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HEK293 Cells
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HL-60 Cells
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Histone Acetyltransferases / metabolism
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Histones / chemistry
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Histones / metabolism
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Humans
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Jumonji Domain-Containing Histone Demethylases / genetics
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Jumonji Domain-Containing Histone Demethylases / metabolism*
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K562 Cells
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LIM Domain Proteins / genetics*
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Leukemia, Promyelocytic, Acute / genetics*
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Leukemia, Promyelocytic, Acute / metabolism*
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Leukemia, Promyelocytic, Acute / pathology
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Neoplasm Proteins / chemistry
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Neoplasm Proteins / metabolism
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Oligonucleotide Array Sequence Analysis
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Oncogenes
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Promoter Regions, Genetic
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Proto-Oncogene Proteins / genetics*
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Recombinant Proteins / genetics
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Recombinant Proteins / metabolism
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Transcriptional Activation
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Tretinoin / pharmacology
Substances
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Adaptor Proteins, Signal Transducing
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DNA, Neoplasm
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Histones
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LIM Domain Proteins
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LMO2 protein, human
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Neoplasm Proteins
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Proto-Oncogene Proteins
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Recombinant Proteins
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Tretinoin
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Jumonji Domain-Containing Histone Demethylases
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KDM3B protein, human
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Histone Acetyltransferases