This entry represents the GATA family of transcription factors, such as GATA-4, GATA-5 and GATA-6. These transcription factors regulate critical steps of cellular differentiation during vertebrate development. GATA-4, 5 and 6 each contain two GATA-type zinc fingers, and are known to activate numerous enterocytic genes [, ]. Loss of GATA-4 and GATA-5 has been reported in human gastric and colon cancer []. GATA-4 binds to the consensus sequence 5'-AGATAG-3', and acts as a transcriptional activator of Anf in cooperation with Nkx2-5 []. It interacts with the homeobox domain of Nkx2-5 through its C-terminal zinc finger. It also interacts with Jarid2 which represses its ability to activate transcription of Anf. Defects in GATA-4 are the cause of atrial septal defect type 2 (ASD2) (OMIM:607941)[]. ASD2 is a congenital heart malformation characterised by incomplete closure of the wall between the atria resulting in blood flow from the left to the right atria.GATA-5 binds to the functionally important Cef-1 nuclear protein binding site in the cardiac-specific slow/cardiac troponin C transcriptional enhancer []. It may play an important role in the transcriptional program(s) that underlies smooth muscle cell diversity.
Chisel protein plays a role in the regulatory network through which muscle cells coordinate their structural and functional states during growth, adaptation, and repair. The X-linked gene Chisel (Csl/Smpx) was first found expressed selectively in human cardiac and skeletal muscle cells []. It is expressed in embryos in sub-regions of the developing heart corresponding to the future chamber myocardium and in developing skeletal muscles []. It is a potential target of the cardiac homeodomain transcription factor Nkx2-5 []. It localises to the costameric cytoskeleton of muscle cells through its association with focal adhesion proteins, where it may participate in regulating the dynamics of actin through the Rac1/p38 kinase pathway [].
Developmental pluripotency-associated protein 2 (Dppa2, also known as ECAT15-2) and Dppa4 (also known as ECAT15-1) have a common DNA binding domain known as the SAP motif. Dppa2 has been found to bind to the regulatory region of Nkx2-5 in embryonic stem (ES) cells []. Dppa4 has been found to bind to both DNA and histone H3 necessary for the chromatin structure resistance to MNase and for the proper localization of Dppa4 in ES cell nuclei [].
Developmental pluripotency-associated protein 2 (Dppa2, also known as ECAT15-2) has a DNA binding domain known as the SAP motif. Dppa2 has been found to bind to the regulatory region of Nkx2-5 in embryonic stem (ES) cells [].
Homeobox genes play fundamental roles in specifying cell fate and positional identity in embryos. Homeobox gene Csx/Nkx2.5, one of the vertebrate homologues of Drosophila tinman, is expressed in the precardiac mesoderm and in the myocardium of the embryonic and adult heart [, ]and is one of the master regulators of cardiac development, homeostasis and disease [, ]. Csx associates with the transcription factor GATA4 and this interaction may regulate a subset of cardiac muscle-specific genes []. Nkx2-5 regulates the gene encoding the Kcnh2 channel [].Mutations of the human Nkx2.5 gene cause congenital heart disease ASD7, characterised by incomplete closure of the wall between the atria [, , ].
