Transcriptional regulation of C/EBPa expression
Final Report Abstract
The study so far has focused on the regulation of C/EBPα transcription by ZNF143 or its mouse homologue ZFP143. As outlined in the grant proposal, we have generated mice with a conditional mutation of the ZFP143 gene based on a gene trap clone obtained from the German Gene Trap Consortium. We have now studied these mice and found initial evidence of an effect on C/EBPα expression. However, the mouse model proved not to be very helpful for conditional mutation of ZFP143 in myeloid cells, due to the fact that even the inactive form of the conditional gene trap was early embryonic lethal. Recent reports by other study groups suggest an early requirement of ZFP143 in embryonic stem (ES) cell growth and maintenance of pluripotency (Chen, 2008), a finding that is in line with the phenotype that we observe. We are still using this model to study the importance of ZFP143 expression for maintenance of ES cell growth and pluripotency, as well as its impact on in vivo expression on its putative target Nanog. To address the importance of ZFP143 specifically for transcriptional activation of the C/EBPα gene we have now generated a classical conditional knock-out construct that we will use to generate mice with Cre-driven conditional deletion of ZFP143.
