Description): The objective of this proposal is to understand molecular mechanisms involved in the regulation of transcription in early vertebrate development. Normal development results from an exceedingly complex hierarchy of regulatory interactions -- many at the transcriptional level. The amphibian, Xenopus laevis is an ideal experimental organism for this study as it offers both an excellent, well- established biochemical system and thoroughly characterized, external development. The candidate s long term career goals are to establish an independent research group and to study developmental regulation of gene expression at the molecular level. Of particular interest are regulatory mechanisms imposed by chromatin -- with a special emphasis on post- translational modifications of the core histones. Recent experiments have underscored and highlighted tested observations demonstrating a direct and potentially causal relationship between active transcription and histone modification.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Career Transition Award (K22)
Project #
1K22HD001238-01
Application #
2744674
Study Section
Special Emphasis Panel (ZHD1-DRG-D (05))
Program Officer
Klein, Steven
Project Start
2000-09-25
Project End
2002-08-31
Budget Start
2000-09-25
Budget End
2001-08-31
Support Year
1
Fiscal Year
2000
Total Cost
$145,001
Indirect Cost
Name
Emory University
Department
Pathology
Type
Schools of Medicine
DUNS #
042250712
City
Atlanta
State
GA
Country
United States
Zip Code
30322
Horton, John R; Elgar, Stuart J; Khan, Seema I et al. (2007) Structure of the SANT domain from the Xenopus chromatin remodeling factor ISWI. Proteins 67:1198-202
Bowen, Nathan J; Fujita, Naoyuki; Kajita, Masahiro et al. (2004) Mi-2/NuRD: multiple complexes for many purposes. Biochim Biophys Acta 1677:52-7
Fujita, Naoyuki; Jaye, David L; Kajita, Masahiro et al. (2003) MTA3, a Mi-2/NuRD complex subunit, regulates an invasive growth pathway in breast cancer. Cell 113:207-19
Georgel, Philippe T; Horowitz-Scherer, Rachel A; Adkins, Nick et al. (2003) Chromatin compaction by human MeCP2. Assembly of novel secondary chromatin structures in the absence of DNA methylation. J Biol Chem 278:32181-8
Aoyagi, Sayura; Wade, Paul A; Hayes, Jeffrey J (2003) Nucleosome sliding induced by the xMi-2 complex does not occur exclusively via a simple twist-diffusion mechanism. J Biol Chem 278:30562-8
Li, Jiwen; Lin, Qiushi; Wang, Weidong et al. (2002) Specific targeting and constitutive association of histone deacetylase complexes during transcriptional repression. Genes Dev 16:687-92
Wade, P A (2001) Methyl CpG binding proteins: coupling chromatin architecture to gene regulation. Oncogene 20:3166-73
Wade, P A (2001) Transcriptional control at regulatory checkpoints by histone deacetylases: molecular connections between cancer and chromatin. Hum Mol Genet 10:693-8
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