Lecture notes

Lecture notes BIOL3015 Transcriptional Regulation

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Lecture notes from BIOL3015 Regulation of gene expression, transcriptional regulation. Covering: regulatory circuits, negative feedback, toggle switch circuits, somitogenesis oscillator, circadian clocks, transcriptional circuits of fruit flies, transcriptional circuits of mammalian clocks, transcr...

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Uploaded on December 11, 2023
Number of pages 10
Written in 2021/2022
Type Lecture notes
Professor(s) Karen lillycrop
Contains Biol3015 transcriptional regulation

gene
gene expression
regulation
transcription
negative feedback
clocks
fruit fly
zoology
biology
mammalian
cell cycles
transcriptional regulation

Institution University of Southampton (UOS)
Education Unknown
Module Unknown

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Transcriptional Regulation
Example regulatory circuits
 Simple negative feedback – homeostasis
 Toggle switch – choice and commitment
 Cycle – alternation of multiple states
Simple negative feedback
 An activity leads to inhibition of said activity
 Gene produces activator that activates promotor of repressor which activates
promotor that stops the activator – maintains balance
 Steady state created
 External influence can change balance
 Chaperone proteins assist in folding of proteins
 A stress can cause an unfolding protein response
 Chaperone recognises protein with hydrophobic surfaces facing outwards
 Chaperones bind to correct unfolding
 Hsp70 normally binds to Hsf1 transcription factor
which keeps Hsp70 inactive as the transcription
factor cannot bind to activation site
 In presence of unfolded protein, transcription
factor releases Hsp70
 More Hsf1 which activates the gene to produce
Hsp70
 Once the cell is oversaturated with Hsp70, it
begins to bind to Hsf1 again which reduces the
production of Hsp70 bringing the ratio back to
balanced
 In healthy neurones, HSF1 is important in
multiple proteins which are for cell survival and
maintenance
 In certain diseases, unfolded protein responses
can be mimicked so the system cannot return
to equilibrium
 Huntington's disease, develops sequences that
act on proteins which are important for HSF1 –
capacity to deal with stress responses is reduced
Toggle switch circuit
 Two possible mutually exclusive outcomes
 Two genes each encode proteins that enhance the
function of the gene but reduce the function of the other
gene
 Whichever gene gains advantage will have the function
amplified
 If b inhibits c and c inhibits b, if you have more b then c is
inhibited, and more b is produced or vice versa
 Two steady states the system can be in
 Bacteriophage lambda – can lysogeny (co-existence) or lysis (murder) the cell

,  The bacteriophage can stay in the cell and merge DNA and the switch to lysis state
and releases bacteriophages killing the cell
 Both advantages in certain scenarios – if lots of host bacteria cells available then lysis
more effective, however, if fewer host cells available then lysogeny is more effective
 Bidirectional promoter (lambda switch region) – transcription proceeds via Prm
(producing C1) or Pr region (producing cro)
 If cro is produced then a homeodimer of 2
cro which promotes expression of cro and
inhibits the expression of c1
 If c1 produced a homeodimer of c1 promotes
the expression of c1 and inhibition of cro
 Both act on PL promotor locus, if more cro
then C3 inhibited, if more c1 then c3
expressed
 C3 degradation reaction inhibits c2
degradation
 Cro produces C2 and C2 activates a promotor
that is in the same orientation as C1
 However, C2 is unstable so does not affect reaction unless C3 is present to stabilise it
 Cro promotes lysis state and c1 promotes lysogeny state
 Whichever produces more, in the beginning, gains the switch and maintains
production
Cycles of transcription
 Data encoded using biological cycles
 Repressilator – 3 bacterial repressors which
each activator by repressor sensitive
promotors
 If one repressor is made then promotor of
another repressor is activated, which in turn
activates the promotor of the next repressor
forming a cycle as each is toggled on and off
Real examples of transcriptional cycles
 Somitogenesis
 Circadian clock
 Cell cycle
Properties of Somitogenesis Oscillator
 Rhythm in Presomitic mesoderm (PSM) cells
 Fixed number of cycles
 Rhythm across cells
 Fixed periodicity – 6 hours humans, 2 hours mouse, 30 min zebrafish
 Somites emerge from tail end
 Clock and wavefront model – assumes there is a gradient and a clock periodic signal
– slower level of oscillation causes slower bigger fewer somites, increased speed of
oscillation causes smaller and more somites
 Hes6 mutant in zebrafish causes slower somite clock oscillation and hence fewer
somites form
 Her1 marks somites

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