For normal organ and tissue development and function, certain genes must be expressed at the appropriate place and time. For example, neural genes must be expressed in neural tissue but shut down in nonneural tissues. Lunyak et al. examined mechanisms by which neural-specific gene expression can be restricted from nonneural tissues. The zinc-finger transcription factor REST/NRSF can mediate extraneural restriction through two different mechanisms, one of which uses active repression via a histone deacetylation complex and one that involves gene silencing via DNA methylation and the recruitment of the corepressor CoREST and silencing machinery. The latter mechanism can mediate gene silencing of specific chromosomal regions, including gene clusters encompassing neuron-specific genes, some of which do not themselves contain REST/NRSF response elements.
V. V. Lunyak, R. Burgess, G. G. Prefontaine, C. Nelson, S.-H. Sze, J. Chenoweth, P. Schwartz, P. A. Pevzner, C. Glass, G. Mandel, M. G. Rosenfeld, Corepressor-dependent silencing of chromosomal regions encoding neuronal genes. Science 298, 1747-1752 (2002). [Abstract] [Full Text]