Transcription enhancer factor-1 (TEF-1) DNA binding sites can specifically enhance gene expression at the beginning of mouse development.

Abstract

In an effort to identify transcriptional elements that are recognized at different stages of early mouse development, polyomavirus (PyV) enhancer mutations were selected for their ability to support PyV transcription and replication in various mouse undifferentiated embryonal carcinoma (EC) and embryonic stem (ES) cell lines. Several of these enhancer mutations were then isolated, sequenced and tested for their ability to stimulate the PyV early gene promoter in plasmid DNA that was either transfected into EC, ES and fibroblast cell lines, or injected into the nuclei of mouse 1‐cell and 2‐cell embryos. EC, ES and fibroblast cell lines showed clear preferences for different enhancer configurations, and cleavage‐stage embryos (2‐ to 8‐cell stage) strongly preferred the same enhancer configuration favored by ES cells. This ‘embryo responsive’ (ER) enhancer configuration was characterized by a tandem duplication of the region containing a single point mutation that created a DNA binding site for Transcription Enhancer Factor‐1 (TEF‐1). ER enhancers stimulated the PyV promoter up to 350‐fold in embryos, and were up to 74‐fold more active than the wild‐type PyV enhancer. Most of the activity from PyER enhancers could be duplicated in 2‐cell embryos by synthesizing only the tandemly repeated sequence. Comparison of these synthetic enhancers with ER enhancers confirmed that TEF‐1 DNA binding sites were highly preferred in ES cells and cleavage‐stage embryos, and suggested that ER enhancer activity resulted primarily from cooperative interaction between either two closely spaced TEF‐1 DNA binding sites or two TEF‐1 DNA binding sites separated by a third, as yet unidentified, transcription factor binding site. These results provide a prototype of a mammalian embryo responsive enhancer, and suggest that TEF‐1 plays an important role in activation of gene expression at the beginning of mammalian development.

Divergent transcriptional enhancer factor-1 regulates the cardiac troponin T promoter

“…TEF-1 multigene family members function in the 2-to 8-day cell stage murine embryo (25), in which knockout produces embryonic lethality due to myocardial hypoplasia (6). In mammals and other vertebrates, TEF-1 factors contribute to MCAT binding activities to regulate muscle-and non-musclespecific gene expression.…”

DNA Methylation May Restrict but Does Not Determine Differential Gene Expression at the Sgy/Tead2 Locus during Mouse Development

“…Tead2 (TEF-4), like other Tead genes, is expressed to various extents in many cells and tissues (references 17 and 18 and references therein). However, Tead2 is the only Tead gene expressed in mouse embryos during the first 7 days of development (17,50), suggesting that it plays a unique role at the beginning of mammalian development by allowing preimplantation mouse embryos to utilize Tead-dependent promoters and enhancers (17,24,26). Sgy is a novel single-copy gene whose mRNA start site is located only 3.8 kb upstream of the Tead2 mRNA start site (19).…”

Physical Interaction between the MADS Box of Serum Response Factor and the TEA/ATTS DNA-binding Domain of Transcription Enhancer Factor-1

“…A TEF-1 homologue, scalloped, in Drosophila, has been shown to play an important role in the lineage progression of sensory neuronal development (32). In mammals, functional TEF-1 is found as early as 2-8 cell stage in the mouse zygote development, and inactivation of TEF-1 gene has been shown to result in embryonic lethality due to myocardial defects (33,34).…”