L15: Regulation of transcription II Flashcards

1
Q

Sequences for regulation of transcription found distal to start site

A
  • Enhancer sequences
  • Often contain high density of sites for binding of regulatory proteins
  • Either upstream or downstream of the gene
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2
Q

Histone acetylation

A
  • Hypoacetylation: Strong inter-nucleosomal interactions; histone tails constrain wrapping of DNA on nucleosome surface (HDACs)
  • Hyperacetylation: Weak inter-nucleosomal interactions: hsitone tails do not constrain DNA, accessible to TFs (HATs)
    -> acetyl grps can also directly recruit proteins via bromodomain proteins
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3
Q

Chromatin remodelling complexes

A
  • e.g. SWI/SNF
  • Use ATP to move the histone octamer
  • They can be recruited either sequence-specifically or by histone modification
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4
Q

Conditions associated w/ changes in methylation pattern

A
  • Fragile X syndrome
  • Cancer
  • During ageing
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5
Q

Interaction between DNA methylation and histone modification

A
  • Methyl groups on either DNA or histone tails can recruit methyl-binding proteins which serve to recruit other proteins that modify chromatin
    -> affects gene expression
  • Various other interactions occur
    -> very complex interactions
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6
Q

DNA methylation and transcriptional control

A
  • Methlyation affects chromatin structure and transcription
  • In the DNA of some euks, cytosine residues are methylated at CpG sites
    -> transcriptionally active genes - lower levels of DNA methylation
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7
Q

The mediator complex

A
  • As well as general transcription factors, RNA pol II requires the Mediator Complex
  • Consists of approx. 20 proteins and is 1 MDa in size
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8
Q

ELK1 ( in absence vs presence of mitogens)

A
  • In the absence of mitogens, ELK1 binds to serum response factor (SRF) but doesn’t activate transcription
  • Mitogen-activated signal transduction pathways phosphorylate ELK1
  • pELK1 recruits mediator, promoting transcription
    -> expression of proliferative genes
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9
Q

GAL genes in yeast (overview)

A
  • GAL1, GAL7, GAL10 encode enzymes that function in a pathway to metabolise galactose (whilst this is analogous to the lac operon, operons are almost never found in eukaryotes)
  • W/out galactose, no transcription, similarly when glucose is available (exerts catabolite repression)
  • Galactose available, glucose not available: rapid transcription
  • GAL4: regulatory protein binds to UASG (upstream activator sequence-galactose)
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10
Q

Inducible transcription process in GAL genes

A
  • Gal4 activates transcription by binding to UASG sequence
  • In absence of galactose, Gal80 binds to Gal4, preventing transcription
  • When galactose present, Gal3 binds to Gal80, preventing Gal80 binding to Gal4
    -> Ga4 recruits SAGA and Mediator (activates transcription)
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11
Q

Nuclear receptor proteins

A
  • Bind to particular signalling molecules (>50 in humans) e.g. oestrogen receptor
  • Ligand binding leads to a conformational change that allows them to drive transcription
  • in some cases binding to the ligand allows translocation to the nucleus e.g. the glucocorticoid receptor
    -> 2 levels (whether they interact w/ corepressor etc. and where in cell they are)
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12
Q

Transcriptional repression in nutrient sensing in yeast

A
  • W/ sufficient N, C source; Ume6 binds DNA and recruits co-repressors (Sin3, Rpd3, Isw2)
  • Rpd3: Histone deacetylase
  • Isw2: nucleosome remodelling enzyme
  • W/out sufficient , C; Ume6 phosphorylated, Sin3 and Rpd3 dissociate, Ime1 (co-activator) recruited
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13
Q

Promoter proximal stalling

A
  • Promoted by negative elongation factors (e.g. NELF, DSIF)
  • Occurs after RNA pol II has transcribed 35-50 bps
  • Relief of this pausing allows transcriptional elongation to proceed (RAPID response to change)
    e.g. expression of gene that encodes Drosophila Hsp70 protein (chaperone that protects cells from high temperatures)
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14
Q

hsp70 transcription (w/ vs w/out heat shock)

A
  • w/out heat shock, GAGA TFs bind and recruit NURF (nucleosome remodelling factor) -> exposes control elements (TATA, HSE). However, negative elongation factors (NELF, DSIF) prevent phosph. of Rpb1 C-term domain
  • w/ heat shock: temperature rise causes Hsf to form a trimer, which binds to HSE sequence, and interacts w/ Mediator to recruit a kinase and CTD is then phosph., relieving pausing
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