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 demonstrated the necessity of chromatin assembly to be coupled to DNA replication to effect repression of basal transcription in vivo. 2. We have made the first determination of specific histone-DNA contacts within a nucleosome incorporating a functional eukaryotic gene. The information leads to a new model for the nucleosome incorporating an asymmetric interaction of histone H1. 3. We have demonstrated that the developmentally regulated replacement of histone variants during vertebrate embryogenesis has functional significance. 4. The Y-box proteins have been shown to mediate not only the accumulation of mRNA from promoters containing their recognition element, but also to direct translational repression in vivo. This is the first reconstruction of `masked mRNA' under controlled conditions. 5. The thyroid hormone receptor has been shown to activate genes encoding metalloproteinases and to repress genes encoding intestinal fatty acid binding protein during amphibian metamorphosis.

Project Start
Project End
Budget Start
Budget End
Support Year
3
Fiscal Year
1993
Total Cost
Indirect Cost
City
State
Country
United States
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