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. Molecular characterization of the Mi-2 complex enable linkage between the chromatin remodeling activities of the SWI/SNF superfamily of ATPases and the targeted deacetylation of histones on methylated DNA. Key components of the Mi-2 complex include the methyl CpG binding componenst MBDB and Mta1 alike.2. The protein-protein interactions that link the methyl CpG binding protein MeCP2 and the associated protein SIN3 to histone deacetylation have been delimeated. SIN3 makes contact with RbAp48 and the RPD3 deacetylase, RbAp48 makes contact with SIN3, RPD3 and with a specific helix within H4. We can reconstruct a chain of protein contacts that enable targeting of histone deacetylase to methylated nucleosomal DNA.3. During early vertebrate development there are major transitions in chromatin structure and in the capacity of the transcriptional machinery to function. We find that both Polycomb group proteins and components of the basal transcriptional machinery are encoded by masked maternal mRNAs. Translational regulation of these mRNAs has an important role in the establishment and maintenance of stable states of gene activity.
| 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 |
