Transcription factors and the cardiac gene programme.

During the past decade, major advances have been made in uncovering the mechanisms that switch genes on and off. Gene methylation and histones play an important role in gene (in)activation. Following gene activation, the initiation of transcription by RNA polymerase requires the assembly of multiple protein complexes on the promoter region of a gene. How a cell type-specific gene expression pattern can be induced is a key question in cardiovascular biology today. Members of the helix-loop-helix-family of the transcription factors play a dominant role in skeletal muscle formation. In cardiac muscle the situation is less obvious. Recent studies identified muscle transcription factors like MEF-2, TEF-1 and MNF, which are common to both the skeletal and cardiac muscle lineages. A few transcription factors, among which Nkx 2.5 and GATA-4, are expressed predominantly in the heart. The absence of master regulators in the heart points to the importance of interaction between ubiquitous factors and tissue restricted factors to initiate the cardiac gene programme and to lock these cells in their differentiated state. The recent development of murine transgenic and gene-targeting technology provides tools to study the role of mammalian transcription factors in vivo. Interesting cardiac phenotypes are found in gene targeted mice, indicating a crucial role for retinoic acid and homeobox genes in murine cardiogenesis.