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.
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Received 05 December 2008; received after revision 18 March 2009; accepted 27 March 2009
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Supplemental data 1.
Excel file for the 1779 probes/genes subjected to the clustering analysis. The cluster designation and time dependent change in expression level for each gene are shown. (XLS 5.99 MB)
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Limb, JK., Yoon, S., Lee, K.E. et al. Regulation of megakaryocytic differentiation of K562 cells by FosB, a member of the Fos family of AP-1 transcription factors. Cell. Mol. Life Sci. 66, 1962–1973 (2009). https://doi.org/10.1007/s00018-009-8775-5
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DOI: https://doi.org/10.1007/s00018-009-8775-5