Lecture 6 Chromatin and Gene Expression

Lecture 6 Chromatin and Gene Expression - Chromatin...

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Chromatin structure and gene expression 1 Monday, September 12, 2011
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Last time 1. Three phases of prokaryotic DNA replication (experiment: deFning the origin of replication) 2. Replication of mtDNA 3. Replication in Eukaryotes 2 Monday, September 12, 2011
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How telomerase works Fig 21.34 TERT TERC 3 Monday, September 12, 2011
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How telomerase works (continued): Fig 21.34 note that there will always be an overhang after removal of primer! 4 Monday, September 12, 2011
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BRIEF COMMUNICATIONS to human chromosomes 3p26.1, 10q26.13, 12q12.22 and 14q23.2 (refs. 3–5). A recent genome-wide association study (GWAS) iden- tified associations of two SNPs on chromosome 18q12.2 with telo- mere length, although the associations were not at a genome-wide significant level 6 . To identify additional variants that affect telomere length, we undertook genome-wide association analyses in two large European cohorts followed by replication of promising signals in three further European cohorts. The discovery cohorts comprised 1,487 individuals with coronary artery disease from the British Heart Foundation Family Heart Study (BHF-FHS) 7 and 1,430 United Kingdom Blood Service donors (UKBS) 8 for whom there was genome-wide SNP genotype data available that was generated using the Affymetrix 500K array as part of the Wellcome Trust Case-Control Consortium (WTCCC) study 8 . Further details of Common variants near TERC are associated with mean telomere length Veryan Codd 1,11 , Massimo Mangino 2,11 , Pim van der Harst 1,3,11 , Peter S Braund 1 , Michael Kaiser 1 , Alan J Beveridge 1 , Suzanne Rafelt 1 Jasbir Moore 1 , Chris Nelson 1 , Nicole Soranzo 2,4 , Guangju Zhai 2 , Ana M Valdes 2 , Hannah Blackburn 4 , Irene Mateo Leach 3 , Rudolf A de Boer 3 , Masayuki Kimura 5 , Abraham Aviv 5 , Wellcome Trust Case Control Consortium 10 , Alison H Goodall 1 , Willem Ouwehand 6 , Dirk J van Veldhuisen 3 , Wiek H van Gilst 3 Gerjan Navis 7 , Paul R Burton 8 , Martin D Tobin 8 , Alistair S Hall 9 , John R Thompson 8 , Tim Spector 2,11 & Nilesh J Samani 1,11 Nat Gen (2010) 42: 197 5 Monday, September 12, 2011
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Telomerase-based anti-aging therapies? • Not so fast. ... • Mice that O/E telomerase - get cancer and die. • Mice that have mutated telomerase - do not age faster that wild type mice (other studies refute this) • One the other hand. ... • If you Frst make the mice resistant to cancer, O/E telomerase DOES make them live longer Cell 135 (4): 609 (2008) • Turning on telomerase has been shown to “reverse” tissue degradation in telomerase mutant mice Nature 469, 102–106 (2011) 6 Monday, September 12, 2011
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Important points • Because no DNAP can attach nucleotides to a 5’, linear chromosomes must necessarily become shorter with each replication
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Lecture 6 Chromatin and Gene Expression - Chromatin...

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