Transcriptional enhancer factor 1 disruption by a retroviral gene trap leads to heart defects and embryonic lethality in mice.

Abstract

We have used a retroviral gene trap in embryonic stem (ES) cells to derive a recessive embryonic lethal mouse strain, ROSA~-geo5. Mutant embryos display an enlarged pericardial cavity, brachycardia, a dilated fourth ventricle in the brain, and die between embryonic days 11 and 12. Whereas heart development in the mutant embryos is extensive, the ventricular wall is abnormally thin with a reduced number of trabeculae. Cloning of the trapped gene indicates that proviral insertion creates a null mutation in the transcriptional enhancer factor 1 (TEF-1) gene. Although transcription of a number of muscle-specific genes believed to be TEF-1 targets appears normal, the defect in cardiogenesis is likely attributable to diminished transcription of one or several cardiac-specific genes.

Transcription factor TEAD2 is involved in neural tube closure

“…TEAD1 is involved in cardiovascular development (Chen et al, 1994). TEAD4 is involved in preimplantation development (Yagi et al, 2007), and TEAD2 is involved in brain development (this report).…”

“…This conservation of structure is reflected in the ability of these proteins to bind the same transcriptional coactivator proteins (Mahoney et al, 2005;Vassilev et al, 2001) and to substitute for TEAD proteins in other organisms (Deshpande et al, 1997). Nevertheless, despite their structural similarities, the four mammalian TEAD proteins are not functionally redundant, because mice lacking TEAD1 fail to develop a proper heart and die between embryonic day 11 (E11) and E12 (Chen et al, 1994), whereas mice lacking TEAD4 arrest development before E3.5 (Yagi et al, 2007). Here we address the role of TEAD2.…”

Factors controlling cardiac myosin-isoform shift during hypertrophy and heart failure

“…(iv) Factors that binds to M-CAT sequences, named TEF1 isoforms; they make a complex with SRF and MEF2 and are found to be necessary for muscle-specific expression of genes in both the cardiac and skeletal muscle-cell context. However, gene ablation of factors such as TEF1, GATA4, and Nkx2.5 has been found to have no effect on the expression of MHCs, while some proteins expressed in the cardiac muscle cell background, such as MLC2 and ANF, were found to be absent in Nkx2.5 null mice [39][40][41][42][43][44][45][46]. SRF knock-out was shown to attenuate the expression of both α-and βMHC transcripts [47].…”

Sequential expression of the MAD family of transcriptional repressors during differentiation and development

“…Human Max9 (Blackwood and Eisenman, 1991) was used to detect murine transcripts. To isolate a murine Mxi1 cDNA for use as a probe, a human Mad1 cDNA was employed to screen a murine AB1 embryonic stem cell cDNA library (Chen et al, 1994). The largest resulting clone (2.3 kb) was subcloned into pGEM-7Zf(+), and upon sequencing was found to contain the entire open reading frame of Mxi1.…”