Download presentation

Presentation is loading. Please wait.

Published byEllen Bryant Modified over 3 years ago

1
A binds independently from other TFs A activates = a/(1+a) A represses = 1/(1+a) A represses, B activates = b/(1+a+b+ab) A and B compete for the same site A and B activate = (a+b)/(1+a+b) A represses, B activates = b/(1+a+b) A and B repress = 1/(1+a+b) B binds to bound A (compulsory order binding) B activates activator A = ab/(1+a+ab) B represses activator A = a/(1+a+ab) B activates repressor A = (1+a)/(1+a+ab) A and B bind as a complex A and B form a hetero- oligomeric activator = ab/(1+ab) A forms a homo- oligomeric activator = a n /(1+a n ) A, B, and C, form a complex repressor = 1/(1+a n b m c k ) Active configurations Logical equivalent Expression for Weights 0ABAB W0W0 WAWA WBWB W AB --- X A BA B 0001 - XXX A B + (1- ) 011 - X -- A BA B (1- ) 010 The Logic of Gene Regulation Maria J. Schilstra & Hamid Bolouri Biocomputation Research Group, University of Hertfordshire, Hatfield, UK http://strc.herts.ac.uk/bio/maria/NetBuilder/index.html Introduction: bio-logic Informal descriptions of experimental observations on gene expression patterns often translate readily into the language of formal logic: Informal statement Proposed logical equivalent 1) “Transcription factors A and B are both necessary for the expression of gene G” G = A B “Either of the transcription factors A or B is sufficient for expression of gene G” G = A B “Expression of gene G is stimulated by A but repressed by B” G = A B 1) : logical AND, : logical OR, : logical NOT operators Questions 1. How do these logical operations relate to the biochemistry of gene expression? 2. Do the rules of Boolean algebra hold for ‘bio-logical’ operations? 3. Is the logical approach always justified? Transcription initiation: a minimal model Transcription factors (TFs) bind to their cis-regulatory binding sites, where they somehow affect the transcription initiation rate. A B A B RNApol The transcription initiation rate k initiation is determined by: 1.The maximum initiation rate (k iniMax ) 2.The occupancy of the TF binding sites (y 0, y A, y B, y AB ) 3.The extent to which each complex stimulates initiation (w 0, w A, w B, w AB ) A + B - A B ++ No A or B: no initiation Only A: weak stimulation Only B: repression of the effect of other factors A and B together: significant stimulation EXAMPLE: If A and B do not affect each other’s binding (i.e. K A /K A(B) = 1), then the expression for can be linearized to: = W 0 + W A + W B + W AB ( = [B]/(K B + [B]), = [B]/(K B + [B]), W 0 = w 0, W A = w A – W 0, w AB = w AB – (W 0 +W A +W B ) From TF binding to cis-regulatory logic The modulation factor = W 0 + W A + W B + W AB determines the transcription initiation rate. Special cases: 1) A B A B 0 ABAB The expressions for the modulation factor hold for Boolean and continuous values between 0 and 1 The expressions for obey the laws of Boolean algebra (associative, commutative, De Morgan’s, etc.) An expression for can substitute a variable in another expression for . Primitives In the expression for , and are primitive: they cannot be linearized further. If binding of A depends on the presence of bound B, it may be necessary to use a primitive that contains [A] and [B] terms. Below: various primitives. a = [A]/K A, b = [B]/K B Fraction of time that the binding sites for A and B are unoccupied (y 0 ), occupied only with A (y A ), or simultaneously with A and B (y AB ). Different TF combinations stimulate or repress transcription to different extents. Dependence of the dynamics of the concentration of the gene product P on the transcription initiation rate, k initiation : Answers 1. The biochemistry of gene expression relates to combinatorial logic as shown above 2. The rules of Boolean algebra hold for bio-logical operations, but... 3.... strictly speaking, the logical approach is only justified for independent cis-regulatory binding sites. In practice, its use (including the choice of primitives) will depend on the accuracy of the data to be modelled, and on prior knowledge of the system

Similar presentations

OK

Control of Gene Expression Year 13 Biology. Exceptions to the usual Protein Synthesis Some viruses contain RNA and no DNA. RNA is therefore replicated.

Control of Gene Expression Year 13 Biology. Exceptions to the usual Protein Synthesis Some viruses contain RNA and no DNA. RNA is therefore replicated.

© 2018 SlidePlayer.com Inc.

All rights reserved.

Ads by Google

Ppt on scientists and their inventions Ppt on yoga and meditation Ppt on semi solid casting Ppt on kingdom monera organisms Maths ppt on real numbers class 10 Ppt on group 2 elements Ppt on brand marketing group Ppt on etiquettes for students Ppt on antimicrobial activity of ginger Ppt on cse related topics about information