Reference:
864.03.002
Abstract:
One of the most profound and intriguing questions in biology concerns the relationship between genetic diversity and the morphology and biology of different species. The key to understanding this relationship will be found in uncovering the contribution of gene family members to the development of organisms. In recent years it has become clear that the general transcription machinery is not as universally used as once thought, as metazoans in general, and vertebrates in particular, contain general transcription factor paralogs not found in yeast. We have contributed to this change in paradigm by our studies of TATA binding protein (TBP) and TBP-like factor, which are found in eukaryotes and metazoans respectively. The molecular and developmental implications of this diversity in the general transcription machinery are unclear, which we propose to address by an integrated approach using Xenopus oocytes and embryos as a vertebrate model system. To this end we will investigate: 1. The biological roles of TBP, TBP-like factor, and a novel, vertebrate-specific TBP paralog, during embryonic development; 2. Alternative mechanisms of transcription initiation; 3. The interaction between a variable transcription machinery and DNA methylation-dependent transcriptional repression and activation during development. Our approach involves a combination of antisense knockdown experiments, gene expression profiling, biochemical purification, chromatin immunoprecipitation, and exploring the nucleo-protein architecture of promoters in vivo. Studying early embryonic gene regulation provides many opportunities to uncover novel molecular mechanisms in control of gene expression, which are pivotal to the regulatory hierarchy of genes during the earliest stages of embryogenesis, including genes essential for mesoderm and neural induction, and patterning. Understanding these processes is essential to further our knowledge of normal development and disease, including congenital malformation and abnormal growth and differentiation.
PROJECT DETAILS
beginning: 2004.
end: 2009.
Country of research: Netherlands
Counry of funding source: Netherlands
Funding organization: Netherlands Organisation for Scientific Research
Financing: NATIONAL FUNDINGS – 405 600 €