REGULATION OF GENE-EXPRESSION AT THE BEGINNING OF MAMMALIAN DEVELOPMENT AND THE TEAD FAMILY OF TRANSCRIPTION FACTORS

In mouse development, transcription is first detected in late 1-cell e mbryos, but translation of newly synthesized transcripts does not begi n until the 2-cell stage. Thus, the onset of zygotic gene expression ( ZGE) is regulated al the level of both transcription and translation. Chromatin-mediated repression is established after formation of a 2-ce ll embryo, concurrent with the developmental acquisition of enhancer f unction. The mosi effective enhancer in cleavage stage mouse embryos d epends on DNA binding sites for TEF-1, the prototype for a family of t ranscription factors that share the same TEA DNA binding domain. Mice contain al least Four, and perhaps five, genes with the same TEA DNA b inding domain (mTEAD genes). Since mTEAD-2 is the only one expressed d uring the first 7 days of mouse development, ii is most likely respons ible for the TEAD transcription factor activity that first appears at the beginning of ZGE. All four mTEAD genes are er:pressed at later emb ryonic stages and in adult tissues, virtually every tissue expresses a t least one family member, consistent with a critical role for TEAD pr oteins in either cell proliferation or differentiation. The 72-amino a cid TEA DNA binding domains in mTEAD-2, 3, and 4 are similar to 99% ho mologous io the same domain in mTEAD-1, and ail four proteins bind spe cifically to the same DNA sequences in vitro with a K-d value of 16-38 nM DNA. Since TEAD proteins appear to be involved in both activation and repression of different genes and do no: appear to be functionally redundant, differential activity of TEAD proteins must result either from association with other proteins or from differential sensitivity to chromatin packaged DNA binding sites. (C) 1998 Wiley-Liss, Inc.