The transcription factor C/EBP{beta} serves as a master regulator of physiologic cardiac hypertrophy.

摘要

A number of possible mechanisms were investigated to explain how C/EBP/3 might mediate this unique gene signature underlying adaptive cardiac hypertrophy. CITED4, another transcriptional cofactor that functions downstream of C/EBP/3, was shown to be directly upregulated in expression with reductions in C/EBP|3 levels. Indeed, CITED4 overex-pression also induced myocyte proliferation in culture with similar changes in adaptive gene expression.1 C/EBP/3 was also shown to directly interact with serum response factor (SRF) where it antagonizes SRF's effect on expression of genes involved in adaptive hypertrophy, such as GATA4 and a-myosin heavy chain (a-MHC). The linkage with GATA4 is also mechanistically important because this transcription factor was shown to regulate cardiomyocyte proliferation and physiologic hypertrophy.2'3 Loss of SRF or GATA4 with GATA6 each also separately resulted in a complete loss of cardiomyocyte differentiation,4'5 suggesting that SRF, GATA4/6, and C/EBPJ3 might function together as master regulators of physiologic growth and differentiation of cardiomyocytes.