Our work is focussed on the molecular mechanisms responsible for establishing and maintaining stable states of gene expression during vertebrate embryogenesis. Progress has been achieved in the following key areas: 1) We have found the core histone acetylation relieves the repression of basal transcription directed by the core histones. Reconstitution of linker histones into nucleosomal templates represses transcription even when the core histones are acetylated. 2) We have discovered that the basal transcriptional machinery represent targets for the coactivators with histone acetyltransferase activity: p300/CBP, PCAF and TAFII250. 3) Major transitions in nucleoprotein organization on transcriptionally competent promoters occur on meiotic maturation of an oocyte into an egg. We determine that a regulated increase in the efficiency of chromatin assembly underlies this remodeling. 4) The regulated transition in chromatin composition during early vertebrate embryogenesis in which maternal linker histone B4 is replaced with somatic histone H1 is found to determine the duration of the competence of ectodermal cells to respond to inductive signals. 5) DNA methylation is shown to exert a dominant, time-dependent repressive effect on the transcription process, whereby methylation specific DNA binding proteins and chromatin assembly act together to erase the transcriptional machinery from DNA.
| Veenstra, G J; Destree, O H; Wolffe, A P (1999) Translation of maternal TATA-binding protein mRNA potentiates basal but not activated transcription in Xenopus embryos at the midblastula transition. Mol Cell Biol 19:7972-82 |
