fall 09 lecture 25

fall 09 lecture 25 - Different molecular mechanisms of...

Info iconThis preview shows pages 1–7. Sign up to view the full content.

View Full Document Right Arrow Icon
1 4. Protection of active gene promoters from methylation Different molecular mechanisms of control of transcription initiation
Background image of page 1

Info iconThis preview has intentionally blurred sections. Sign up to view the full version.

View Full DocumentRight Arrow Icon
2 Deficiency of CG pairs in genome in general (ave 40%) - mostly present in some promoters - CpG boxes or islands Methyl groups are attached to C in some CG doublets on DNA 4. Protection of promoters of active genes from methylation Elimination of methylated C during evolution through conversion into T Deamination of normal C repair system thinks it’s U, not present in DNA , mutation is recognized it gets repaired Deamination of methylated C repair system thinks it’s T, present in DNA , mutation is not recognized for repair it stays
Background image of page 2
3 Methylation of C in CpG doublets prevents transcription in general : 4. Protection of promoters of active genes from methylation Both DNA and histones can be methylated → generally a sign of inactive chromatin - heterochromatin Methylation affects chromatin structure: Methylated CpGs - recognized by methyl- binding domain proteins (MBP) that can recruit histone-modification enzymes such as histone deacetylase (HDAC) and histone methyl transferase (HMT) - histone deacetylation and methylation - local chromatin will be condensed extensive methylation near (or in) a gene sequence generally prevents (or stops) transcription of that gene
Background image of page 3

Info iconThis preview has intentionally blurred sections. Sign up to view the full version.

View Full DocumentRight Arrow Icon
4 4. Protection of promoters of active genes from methylation CpG islands in promoters of housekeeping genes are preserved as unmethylated → genes are active “Islands” - stretches of 200-500 nucleotides, with GC content (amount of CpG doublets) >50% (different definitions) Islands act either as core promoters or upstream elements How are the promoters of active genes protected from being methylated? Mechanism is still unclear: a) inherent sequence properties prevent binding of DNA methyltransferase (DNMT)? b) existence of demethylase (DM)? c) GTFs and RNAP II + H3 tail modifications exclude the DNMT from sites of transcriptional initiation? FEBS letters, Volume 583, Issue 11, 5 June 2009 , Pages 1713-1720, CpG islands – ‘A rough guide’ Robert S. Illingworth and Adrian P. Bird,
Background image of page 4
5 Methyl groups removed through the creation of new strands-which are not methylated at first - this only occurs during DNA replication. Demethylase existence is postulated (active demethylation is happening as well) but the actual enzyme hasn't been found!!!!! New DNA does get methylated later – enzyme maintenance methylase 4. Protection of promoters of active genes from methylation
Background image of page 5

Info iconThis preview has intentionally blurred sections. Sign up to view the full version.

View Full DocumentRight Arrow Icon
Methylation could turn genes ‘on’ and ‘off’ DEVELOPMENT: CANCER: global hypomethylation and gene specific hypermethylation in the promoter regions of some genes - e.g.
Background image of page 6
Image of page 7
This is the end of the preview. Sign up to access the rest of the document.

Page1 / 26

fall 09 lecture 25 - Different molecular mechanisms of...

This preview shows document pages 1 - 7. Sign up to view the full document.

View Full Document Right Arrow Icon
Ask a homework question - tutors are online