26 - Transcription (Eukaryotes); Initiation by other RNAPs

26 - Transcription (Eukaryotes); Initiation by other RNAPs...

Info iconThis preview shows pages 1–6. Sign up to view the full content.

View Full Document Right Arrow Icon
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
•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 (m5C ) 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 (due to spontaneous deamination) •Deamination of normal C repair system thinks it‟s U, not present in DNA , mutation is recognized U gets repaired •Deamination of methylated C repair system thinks it‟s T, present in DNA , mutation is sometimes not recognized for repair T stays
Background image of page 2
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. 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
•Methyl groups “removed” through the creation of new strands - which are not methylated at first - this only occurs during DNA replication. •New DNA does get methylated later – enzyme maintenance methylase 4. Protection of promoters of active genes from methylation •Demethylase existence is postulated (active demethylation is happening as well) but the actual enzyme hasn't been found!!!!! Biochemical mechanisms implicated in enzymatic DNA demethylation: 1. substitution of one H from the methylated cytosine methyl group with OH (oxidative demethylation) – formation of hydroxymethyl cytosine 2. substitution/repair (!) of the methylated cytosine base by base or nucleotide excision repair 3. deamination of m5C ( T) followed by base excision or mismatch repair
Background image of page 5

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

View Full DocumentRight Arrow Icon
Image of page 6
This is the end of the preview. Sign up to access the rest of the document.

Page1 / 27

26 - Transcription (Eukaryotes); Initiation by other RNAPs...

This preview shows document pages 1 - 6. Sign up to view the full document.

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