CEBPa

CEBPA, or CCAAT/enhancer-binding protein alpha, is a human transcription factor encoded by the CEBPA gene. It belongs to the C/EBP family and is a basic leucine zipper (bZIP) protein that binds CCAAT/enhancer motifs in DNA to regulate transcription. C/EBP alpha controls the development and function of several lineages, most prominently myeloid cells and adipocytes. In hematopoiesis, it acts as a key regulator of granulocytic differentiation, promoting maturation of neutrophils. In adipose tissue, it cooperates with other transcription factors to drive adipogenesis and the expression of adipocyte genes such as FABP4 and adiponectin. In liver and other tissues, C/EBP alpha participates in metabolic gene regulation, including gluconeogenesis and lipid metabolism.

The protein is produced from the CEBPA gene as two main isoforms, p42 and p30, generated by alternative translation initiation. The p42 isoform supports differentiation, whereas p30 lacks the N-terminal activation domain and is linked to proliferative states; the relative balance influences cell fate. C/EBP alpha functions as a dimer and interacts with coactivators such as CBP/p300 and collaborates with other transcription factors including PU.1 and RUNX1 during myeloid development.

Mutations or altered expression of CEBPA are linked to acute myeloid leukemia (AML), particularly biallelic CEBPA mutations, which can affect prognosis and response to therapy. Animal models with Cebpa deficiency exhibit impaired hematopoiesis and liver development, underscoring its essential role. CEBPA thus acts as a critical regulator at the intersection of hematopoiesis, adipogenesis, and metabolism.