13. Control of eukaryotic gene expression 2
- Created by: Alice Fisher
- Created on: 09-05-15 21:48
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- 13. Control of eukaryotic gene expression 2
- Chromatin
- Trans acting transcription factors (activators or repressors) bind to cis acting dna sequence in chromatin
- Chromosomes organised, supercoiled, nucleoprotein, fibrous 3x109 bp
- Building blocks of chromatin are nucleosomes146bp DNA per nucleosome. Wrapped around an octamer of core histones
- Nucleosomescan be covalently modified. Structural changes affects transcription
- Structure; efficient and ordered packaging of large amounts of DNA. Structure makes it difficult for transcription factors to find target genes.
- Histones
- 1. Chromatin remodelling factors - coil and uncoil chromatin fibres (reversible packaging). This move histones along the dna molecules opening and closing access to specific dna sequences
- 2. Covalent modificationsof specific regions on dna and histones "flagged". Direct transcription factors here.
- Nucleosomescan be fixed into position within chromatin by linker histones H1 which facilitates chromatin compaction and organisation but limit accessibility
- CRF displace linker and core histones from stable interaction with dna
- Acetylation of lysin residues in the N terminal tails of core histones. This acts as flags that recruit transcriptional activators keeping genes on
- Methylation of dna in cytosine bases in cpg dinucleotidesis a hallmark of transcriptionally inactive chromatin; helps to switch gene off
- Causes loss of transcription activators. Methylation carried out by enzymes. Causes recruitment of methyl-c binding proteins and hence a repressor
- Methylation of dna in cytosine bases in cpg dinucleotidesis a hallmark of transcriptionally inactive chromatin; helps to switch gene off
- Changes to chromatin structure that effects expression of genes without altering nucleotide sequence are known as epigenetic changes
- Tortoise shell cats exhibit an epigenetic phenotype caused by random epigenetic silencing of the coat colour genes in patches of skin pigment cells
- 1. Chromatin remodelling factors - coil and uncoil chromatin fibres (reversible packaging). This move histones along the dna molecules opening and closing access to specific dna sequences
- Post transcriptionalcontrols
- RNA transcript - splicing - 5' capping polyadenylation - nuclear export - mrna localisation in cytoplasm - mrna translation - mrna stability
- RNA splicing involves removal of introns and the ligation of exons. Controls sex determinationin drosophila
- Transformer protein (only in females) is a splicing activator. Removal of intro (DSXF) results in female. DSXM results in male.
- Alternative splicing controls the synthesis of multiple protein isoforms from a single gene as produce different exon-intron junction in rna transcripts
- 5' cap structure required for translation initiation. Initiation factors regulate translation e.g. phosphorylation
- Translation of mrna encoding the iron storage protein ferritin is positively regulated by the free ion concentration. Low iron; aconitase binds to ferritin mrna and inhibits translation. High; it dissociates so translation can occur
- Chromatin
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