Abstract
The regulation of megakaryocytic differentiation is poorly understood. Using K562 cells, which can partly recapitulate the process in response to phorbol 12-myristate 13-acetate (PMA), we performed microarray-based gene expression profiling to identify genes that play significant roles in megakaryopoiesis. Here, we describe the function of FosB, an AP-1 transcription factor. FosB is induced in PMA treated K562 cells in a sustained manner and forms an active AP-1 protein-DNA complex. Down-regulation of FosB with specific shRNAs inhibited the induction of CD41, a specific cell surface marker of megakaryocytes. We also show that activation of the PKC-MEK-ERK signaling pathway is required for induction of FosB and CD41. Finally, we cross-examined the microarray data in conjunction with gene function annotation data to identify additional target genes of FosB. We define 3 genes, INHBA, CD9, and ITGA2B as regulatory targets of FosB and show that CD9, in particular, is a direct target of FosB.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Antigens, CD / metabolism
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Cell Differentiation / drug effects
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Chromatin Immunoprecipitation
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Down-Regulation
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Gene Expression Profiling
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Humans
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Inhibin-beta Subunits / metabolism
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Integrin alpha2 / metabolism
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K562 Cells
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MAP Kinase Signaling System / physiology
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Megakaryocytes / drug effects
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Megakaryocytes / physiology*
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Membrane Glycoproteins / metabolism
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Oligonucleotide Array Sequence Analysis
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Platelet Membrane Glycoprotein IIb / metabolism
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Protein Kinase C / metabolism
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Proto-Oncogene Proteins c-fos / genetics
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Proto-Oncogene Proteins c-fos / physiology*
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Signal Transduction
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Tetradecanoylphorbol Acetate / pharmacology
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Tetraspanin 29
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Transcription Factor AP-1 / physiology*
Substances
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Antigens, CD
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CD9 protein, human
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FOSB protein, human
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ITGA2B protein, human
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Integrin alpha2
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Membrane Glycoproteins
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Platelet Membrane Glycoprotein IIb
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Proto-Oncogene Proteins c-fos
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Tetraspanin 29
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Transcription Factor AP-1
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inhibin beta A subunit
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Inhibin-beta Subunits
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Protein Kinase C
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Tetradecanoylphorbol Acetate