The FACT chromatin modulator: genetic and structure/function relationships.
The chromatin configuration of DNA inhibits access by enzymes such as RNA polymerase II. This inhibition is alleviated by FACT, a conserved transcription elongation factor that has been found to reconfigure nucleosomes to allow transit along the DNA by RNA polymerase II, thus facilitating transcription. FACT also reorganizes nucleosomes after the passage of RNA polymerase II, as indicated by the effects of certain FACT mutations. The larger of the two subunits of FACT is Spt16/Cdc68, while the smaller is termed SSRP1 (vertebrates) or Pob3 (budding yeast). The HMG-box domain at the C terminus of SSRP1 is absent from Pob3; the function of this domain for yeast FACT is supplied by the small HMG-box protein Nhp6. In yeast, this "detachable" HMG domain is a general chromatin component, unlike FACT, which is found only in transcribed regions and associated with RNA polymerase II. The several domains of the larger FACT subunit are also likely to have different functions. Genetic studies suggest that FACT mediates nucleosome reorganization along several pathways, and reinforce the notion that protein unfolding and (or) refolding is involved in FACT activity for transcription.
Singer
Richard A
RA
Department of Biochemistry & Molecular Biology, Dalhousie University, Halifax, Canada. richard.singer@dal.ca
Johnston
Gerald C
GC
D000483:Alleles; D000818:Animals; D002453:Cell Cycle; D002843:Chromatin / Q000737:chemistry* / Q000378:metabolism; D004247:DNA / Q000737:chemistry; D004268:DNA-Binding Proteins / Q000737:chemistry* / Q000235:genetics / Q000502:physiology*; D016153:Genes, Suppressor; D006609:High Mobility Group Proteins / Q000737:chemistry* / Q000235:genetics / Q000502:physiology*; D008954:Models, Biological; D009154:Mutation; D009707:Nucleosomes / Q000378:metabolism; D011489:Protein Denaturation; D017510:Protein Folding; D017434:Protein Structure, Tertiary; D012319:RNA Polymerase II / Q000737:chemistry / Q000378:metabolism; D004718:Saccharomycetales / Q000502:physiology; D013329:Structure-Activity Relationship; D013696:Temperature; D035602:Transcriptional Elongation Factors / Q000737:chemistry* / Q000235:genetics / Q000502:physiology*
D002843:Chromatin; D004268:DNA-Binding Proteins; D006609:High Mobility Group Proteins; D009707:Nucleosomes; C073537:SSRP1 protein, human; D035602:Transcriptional Elongation Factors; D004247:DNA; D012319:RNA Polymerase II