Chromatin modification has recently emerged as a novel and important mechanism in the regulation of gene expression. However, the impact that chromatin modifiers and the resulting modifications have on molecular networks establishing proper cell-fate and development in multi-cellular organisms are just beginning to emerge. In order to better understand this question, this NRSA will use the C. elegans as an in vivo system to investigate the role of HDA-1 (histone-deacetylase 1) during early embryogenesis by using molecular, biochemical, and genomic approaches. Since HDA-1 is crucial for proper cell-fate determination, the identification of direct HDA-1 target genes and the impact that this protein has on the chromatin environment will be fundamental in understanding the mechanistic role of HDA-1. Based on these exciting findings, new models are likely to emerge about the in vivo function and mechanism of action of histone deacetylases in the development of a multi-cellular organism.
| Iwase, Shigeki; Lan, Fei; Bayliss, Peter et al. (2007) The X-linked mental retardation gene SMCX/JARID1C defines a family of histone H3 lysine 4 demethylases. Cell 128:1077-88 |
| Shi, Yang; Whetstine, Johnathan R (2007) Dynamic regulation of histone lysine methylation by demethylases. Mol Cell 25:1-14 |
| Whetstine, Johnathan R; Ceron, Julian; Ladd, Brendon et al. (2005) Regulation of tissue-specific and extracellular matrix-related genes by a class I histone deacetylase. Mol Cell 18:483-90 |
| Shi, Yujiang; Lan, Fei; Matson, Caitlin et al. (2004) Histone demethylation mediated by the nuclear amine oxidase homolog LSD1. Cell 119:941-53 |
