Repression and activation by multiprotein complexes that alter chromatin structure.

Abstract

Recent studies have provided strong evidence that macromolecular complexes are used in the cell to remodel chromatin structure during activation and to create an inaccessible structure during repression, Although there is not yet any rigorous demonstration that modification of chromatin structure plays a direct, causal role in either activation or repression, there is sufficient smoke to indicate the presence of a blazing inferno nearby. It is clear that complexes that remodel chromatin are tractable in vitro; hopefully this will allow the establishment of systems that provide a direct analysis of the role that remodeling might play in activation. These studies indicate that establishment of functional systems to corroborate the elegant genetic studies on repression might also be tractable. As the mechanistic effects of these complexes are sorted out, it will become important to understand how the complexes are regulated. In many of the instances discussed above, the genes whose products make up these complexes were identified in genetic screens for effects on developmental processes. This implies a regulation of the activity of these complexes in response to developmental cues and further implies that the work to fully understand these complexes will occupy a generation of scientists.

A murine ATFa-associated factor with transcriptional repressing activity

“…Transcriptional repression of eukaryotic gene expression has been appreciated relatively recently (for reviews see Levine and Manley, 1989;Cowell, 1994;Johnson, 1995;Hanna-Rose and Hansen, 1996;Kingston et al, 1996;Kadonaga, 1998). Proteins have been characterized that modulate the chromatin state and may thereby negatively act on template accessibility to the transcription machinery.…”

“…Proteins have been characterized that modulate the chromatin state and may thereby negatively act on template accessibility to the transcription machinery. These include the silencing proteins in yeast (Orlando and Paro, 1995), the Polycomb group gene products in Drosophila (Simon, 1995) or the methylated-DNA-binding proteins in vertebrates (Zhang et al, 1986;Nan et al, 1997) all of which create a repressive chromatin state, as opposed to multiprotein complexes like the yeast SWI/SNF and their metazoan homologues (Winston and Carlson, 1992;Tsukiyama and Wu, 1995) which increase nucleosome mobility (Kingston et al, 1996;Kadonaga, 1998).…”

p53 binds to a constitutively nucleosome free region of the mdm2 gene

“…However the cellular transcription machinery is designed to function with chromatin not naked DNA (reviewed in Felsenfeld, 1996;Kingston et al, 1996). Recently histone acetylases and histone deacetylases have been shown to regulate transcription by recon®guring chromatin (Wol e, 1996;Taunton et al, 1996;Brownell et al, 1996;Wol e and Pruss, 1996).…”

Purification of histone deacetylase HD1‐A of germinating maize embryos

“…Specific mutations in the amino termini have distinct effects on gene activation, silencing and repression [41]. The amino terminal histone tails can be acetylated at certain lysine residues, resulting in a decrease of the net positive charge on one hand, and in an alteration of their specific binding properties for regulatory proteins on the other hand.…”