Transcriptional regulation of bone marrow thrombopoietin by platelet proteins

Platelet production is regulated primarily by the cytokine thrombopoietin (TPO). Although TPO is expressed in several different tissues, only in the bone marrow has the level of expression been reported to increase in response to reduced numbers of platelets. In these studies, we demonstrate that platelet granule proteins are able to transcriptionally repress TPO mRNA expression in a marrow stromal cell line as well as in primary bone marrow stromal cell cultures. Like TPO mRNA, secretion of TPO protein was also suppressed by serum treatment. Reporter gene constructs indicate that DNA elements located in an approximately 1.9-kb region between 250-bp upstream of the transcriptional initiation site and the middle of the second intron are able to mediate the transcriptional repression.