Regulation of gene expression in eukaryotes II. 22 November 2013.

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Regulation of gene expression in eukaryotes II. 22 November 2013

Modular nature of RDBPs

Different ways the activity of RDBPs can be modulated

The same RDBP can activate multiple genes

Additive synergy of activator RDBPs

Fine-tuning of regulation involving RDBPs, co-activators, and co-repressors

Global input involving the various RDBPs bound to an enhancer sequence

Repressor RDBPs reduce transcriptional activity in several possible manners.

Integration of regulatory inputs at the promoter.

7 stripes of even-skipped expression Stripe 2 module driving beta-gal

Cytosine methylation

DNA methyltransferases (methylases) De novo methylases: Dnmt3A DNmt3B Maintenance methylase: Dnmt1

CpG islands

Cytosine methylation and transcriptional activity.

Imprinting

A well known exception.

CpG Islands- Why?

Deamination of 5-methylcytosine produces thymine

A model for the origin of CpG islands Most CG sites methylated except those in proximal promoter CGs 5-methyl C Deamination of 5- methylC gives you a T and the CG has become TG

CpG Islands

« active » chromatin vs « inactive » chromatin ACTIVE CHROMATIN: Decondensed structure, absence of histone H1 Reduced methyl-cytosine (5meC) content. High proportion of hyperacetylated histones « Open » promoter region (free, accessible and RDBPs are bound and they are generally activators) Higher sensibility to nucleases (i.e. DNAse I – presence of hypersensitive DNAse I sites).

Role of Histone H1

« active » chromatin vs « inactive » chromatin ACTIVE CHROMATIN: Decondensed structure, absence of histone H1 Reduced methyl-cytosine (5meC) content. High proportion of hyperacetylated histones « Open » promoter region (free, accessible) Higher sensibility to nucleases (i.e. DNAse I – presence of hypersensitive DNAse I sites).

DNase I Hypersensitive sites

« active » chromatin vs « inactive » chromatin ACTIVE CHROMATIN: Decondensed structure, absence of histone H1 Reduced methyl-cytosine (5meC) content. High proportion of hyperacetylated histones « Open » promoter region (free, accessible) Higher sensibility to nucleases (i.e. DNAse I – presence of hypersensitive DNAse I sites).