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.
Electronic supplementary material
The online version of this article (doi:10.1007/s00018-009-8775-5) contains supplementary material, which is available to authorized users.
Keywords. FosB, AP-1, megakaryocyte, CD41, K562
Electronic Supplementary material
Below are the links to the electronic supplementary material.
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)
Footnotes
Received 05 December 2008; received after revision 18 March 2009; accepted 27 March 2009
Contributor Information
G.-J. Jhon, FAX: 82-2-3277-3760, Email: gjjhon@ewha.ac.kr
J. Kim, FAX: 82-2-3277-3760, Email: jkim1964@ewha.ac.kr
Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials
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)