The long term goals of the Human Cell Genetics Section (HCGS) are: i) to elucidate mechanisms by which determinants of higher order chromatin structure and associated epigenetic mechanisms regulate cell growth and survival; and ii) to relate such cellular control mechanisms to senescence and age-related disease in the intact organism. Of particular interest is the hypothesis that damage and remodeling of chromatin-based structures contribute to mammalian senescence, both at the cellular and organismal levels. One approach to detect such remodeling is a semi-random sampling of genome chromatin structure, DDChIP, a method similar in principle to differential display. Over the past year, a second approach has been added. The latter is based on bioinformatics software developed by the HCGS. Sequence motifs or clusters of motifs are searched for in the human and mouse genomes. Further criteria to define objects of interest include inverted repeats, nearby CpG islands, etc. Loci identified in the two genomes are assessed for conservation by cross-blast analysis. This step eliminates the vast majority of noise in the search results. Lists of candidate loci are submitted for automated primer design and synthesis. Normalized arrays of primer pairs facilitate robot-based PCR assembly. Finally, a novel automated HPLC-based technique for PCR analysis coupled with custom graphics software allows rapid evaluation of the results. Current experiments are exploring the utility of this bioinformatics-experiment interface in pursuing the above stated goals.
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| Golikov, Vladislav; Logacheva, Irina; Bruk, Gennadi et al. (2004) Modelling of long-term behaviour of caesium and strontium radionuclides in the Arctic environment and human exposure. J Environ Radioact 74:159-69 |
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| Oughton, Deborah; Forsberg, Ellen-Marie; Bay, Ingrid et al. (2004) An ethical dimension to sustainable restoration and long-term management of contaminated areas. J Environ Radioact 74:171-83 |
| Bae, Nancy S; Swanson, Mark J; Vassilev, Alex et al. (2004) Human histone deacetylase SIRT2 interacts with the homeobox transcription factor HOXA10. J Biochem (Tokyo) 135:695-700 |
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| Russanova, Valya R; Hirai, Tazuko H; Howard, Bruce H (2004) Semirandom sampling to detect differentiation-related and age-related epigenome remodeling. J Gerontol A Biol Sci Med Sci 59:1221-33 |
| Russanova, Valya R; Hirai, Tazuko H; Tchernov, Andrei V et al. (2004) Mapping development-related and age-related chromatin remodeling by a high throughput ChIP-HPLC approach. J Gerontol A Biol Sci Med Sci 59:1234-43 |
| Reid, Malcolm S; Prichep, Leslie S; Ciplet, Debra et al. (2003) Quantitative electroencephalographic studies of cue-induced cocaine craving. Clin Electroencephalogr 34:110-23 |
| Yamagoe, Satoshi; Kanno, Tomohiko; Kanno, Yuka et al. (2003) Interaction of histone acetylases and deacetylases in vivo. Mol Cell Biol 23:1025-33 |
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