Transition to Open Chromatin Chromatin remodeling complexes like as SWISNF

Transition to open chromatin chromatin remodeling

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Transition to Open Chromatin Chromatin remodeling complexes like as SWI/SNF manipulate nucleosomes o SWI/SNF is recruited to local sites in the genome SWI/SNF either binds to acetylated histone or is recruited to a gene by protein- protein interactions with a pioneering transcription factor Chromatin remodeling complexes alter chromatin structure by: unwrapping DNA from nucleosomes repositioning nucleosomes evicting nucleosomes
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Chromatin remodeling “ spreads ” to surrounding areas of the genome changing accessibility of the DNA for activator proteins Active Promoter Free of Nucleosomes Key concept: combined actions of HATs + chromatin remodeling complexes (i.e. SWI/SNF ) together lead to open chromatin structure transcription start site is devoid of nucleosomes to make room for assembly of the transcription preinitiation complex HATs bind near promoters and act to maintain open chromatin structure Cis-acting Elements in Mammalian Genes Key concept : Mammalian genes have many cis-acting elements that provide binding sites for transcription factors o Some are promoter proximal elements , others called enhancers are at distant locations along the chromosome. transcription start site within promoter region Promoter proximal elements often located upstream o specific transcription factors bind to these sequences Enhancers located at promoter distal positions , cover ~200-500 bp, and contain several different transcription factor binding sites human genome has 21000 protein coding genes, and perhaps as many as one million enhancers! Eukaryotic Sequence Specific DNA Binding Motifs Key concept: Transcription factors = sequence specific DNA binding proteins o These proteins typically have a modular design with a DNA binding domain (DBD) and an activation domain (AD) DBD designed to position recognition helix into major groove forming chemical bonds w/ base pairs. ~ 80% of eukaryotic sequence-specific DNA binding proteins have one of the following motifs : o helix- turn -helix o similar motif called homeodomain o 1/2 zinc finger motifs: classical zinc finger nuclear receptor zinc finger o 1/2 extended dimerization domains motifs: leucine zipper “bZip” proteins helix- loop -helix proteins! Homeodomain Proteins
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Homeodomain motif named for a group of proteins important for developmental processes ( “homeotic” proteins) o Motif is superficially similar to helix-turn-helix o homeodomain has three α helices 3rd helix = recognition helix Classical Zinc-Finger Motif Consensus sequence of classical Zn fingers o … C-X 5 - C-X 3-(F/Y)-X 5-L-X2-3 - H-X3-4 - H … Major structural features are: o 2 strands and an helix o Zn coordinated by 2 cys & 2 his o conserved phe/tyr & leu form a “ strut” positioning the recognition helix .
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  • Spring '08
  • Biochemistry, dna polymerases

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