Transcriptional regulation of C/EBPa expression

• Applicant: Dr. Boris Bartholdy
• Subject Area: Cell Biology
• Term: from 2008 to 2009
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 66086518

Cancers can arise when the normal cell proliferation and/or cell differentiation programs are severely disturbed. Often, this occurs due to changes in the tight regulation of key transcription factors governing these programs. Each one of these regulatory proteins drives the expression of a characteristic set of target genes, thereby instructing cells to adopt a specific fate, to differentiate or to proliferate. Myeloid differentiation is achieved through the activation of specific transcription factors – either by their increased expression, or by their functional activation. C/EBPα is one key transcription factor involved in myeloid differentiation and frequently deregulated in human acute myeloid leukemias (AML), as well as in blast crisis of chronic myelogenous leukemia (CML). Disruption of its function contributes to the the block in differentiation observed in these diseases and thus to leukemogenesis. Here, we have identified two novel mechanisms that appear to regulate CEBPα expression, and could potentially be used as therapeutic targets to control C/EBPα levels: a zinc-finger transcription factor binding the promoter region essential for myeloid development, ZNF143, and a specific microRNA whose expression affects the protein level of C/EBPα, miR-221. We propose to study the contribution of these regulatory mechanisms to the regulation of CEBPα in myelopoiesis and leukemogenesis and to investigate their potential to modulate CEBPα expression in disease states.

• DFG Programme: Research Fellowships
• International Connection: USA
• Host: Dr. Daniel G. Tenen