Molecular Basis for Relationship between Genotype and Phenotype

Molecular Basis for Relationship between Genotype and Phenotype

Molecular Basis for Relationship between Genotype and Phenotype genotype DNA DNA sequence transcription RNA translation

protein function phenotype organism amino acid sequence Eukaryotic Gene Regulation - Transcription

Expression of genes can be: - constitutively on (housekeeping genes ... ~15,000 in humans) - regulated (temporally or spatially ... up to 2000+ unique proteins in differentiated cell) Differentiation is a manifestation of genes being selectively turned off. Regulation of gene expression involves: - cis-acting regulatory elements - trans-acting transcription factors

Cis-acting Regulatory Elements Promoter - located near transcription-initiation site - binds RNA polymerase II Promoter-proximal Elements - located near promoter - binds proteins that assist RNA polymerase binding Distance-independent Elements - enhancers: increase transcription rates - silencers: decrease transcription rates

Promoter and Promoter-proximal Elements In all cells, constitutive expression of transcription factors that bind to upstream promoter elements ensures active transcription at all times. Promoter and Promoter-proximal Elements Effect of point mutations on transcription rate of -globin gene. In general, transcription rate is reduced when base sequence is changed in the core promoter and promoter-proximal elements.

Distance-independent Cis-acting Elements Both enhancers and silencers affect transcription rate. Each has unique DNA sequence for the binding of regulatory proteins. Enhancer sequences contain multiple binding sites for trans-acting regulatory proteins. Enhancers could be located upstream from the promoter, downstream from the gene, or even within an intron of a gene. Distance-independent Cis-acting Elements

Interaction between regulatory proteins that bind to enhancer elements and promoterproximal elements with RNA polymerase initiates transcription at appropriate levels. Architectural proteins allow bending of the DNA to bring all components together,

both spatially and functionally. Regulatory Proteins that Modulate Transcription These proteins contain one or more functional domains: 1. Recognize DNA regulatory sequence 2. Interact with transcriptional apparatus proteins (RNA polymerase, proteins associated with RNA polymerase) 3. Interact cooperatively with other regulatory proteins bound to DNA sequence

4. Influence chromatin condensation 5. Act as sensor of intracellular physiological conditions Transcription Factors Transcription factors have: 1. DNA binding domain (interact with promoter-proximal elements or enhancers/silencers) 2. Transactivation domain (activate or repress transcription, involved in protein/protein interaction)

Structural Families of Transcription Factors and Regulatory Proteins: Helix-Turn-Helix: Many homeotic genes code for TF's of this class. Zinc-Finger: Many steroid hormone receptor protein TF's belong to this class.

Leucine Zipper: Proto-oncogenes such as c-jun and c-fos are genes that encode TF's of this class. Helix-Loop-Helix: Certain proto-oncogenes and genes involved in differentiation encode TF's of this class. Structural Families of Transcription Factors and Regulatory Proteins: Zinc-Finger:

Leucine Zipper: Helix-Loop-Helix:

Recently Viewed Presentations

  • Phys102 Lecture 9 Electric Currents and Resistance Key

    Phys102 Lecture 9 Electric Currents and Resistance Key

    For ohmic devices, we can make the substitutions: Electric Power. Electric Power. Example: Headlights. Calculate the resistance of a 40-W automobile headlight designed for 12 V. Solution: R = V2/P = 3.6 Ω. Current from a battery flows steadily in...
  • CCS 2005-2006 Mini-programme 1 DR KEN NEIL PHILOSOPHY

    CCS 2005-2006 Mini-programme 1 DR KEN NEIL PHILOSOPHY

    In breaking free, the Contemporary artist also breaks free from the idea that the present is destined to be better than the past - which is our myth of the Davey lamp, a myth which excludes questions of true value....
  • Does Prior -block Therapy Reduce CK-MB Enzyme Release During ...

    Does Prior -block Therapy Reduce CK-MB Enzyme Release During ...

    March 20th 2012 Case #19: FE, 61 yrs F Presentation: Patient with prior DES PCIs of LAD and RCA in 2010, presented on 3/2/2012 with cresendo angina CCS class III.
  • Themes in To Kill a Mockingbird - Thomas English 8

    Themes in To Kill a Mockingbird - Thomas English 8

    It's a sin to kill a mockingbird. It is a symbol of innocence. Boo Radley and Tom Robinson are also innocent. What is the author trying to make us think about innocence from the events of this novel? The Gothic...
  • ECAI 02 Invited Plenary Talk - Sebastian Thrun

    ECAI 02 Invited Plenary Talk - Sebastian Thrun

    F T [i] [i] new particle old particle M = Number of particles N = Number of map features O(M) Constant time per particle O(M logN) Log time per particle O(M logN) Log time per particle Kalman: O(N2) 500 features...
  • Community Broadband Access Map Presented to the Virginia ...

    Community Broadband Access Map Presented to the Virginia ...

    Community Broadband Access Map Presented to the Virginia Chapter of the American Planning Association July, 2007 Jean Plymale Virginia Tech eCorridors Program
  • Chapter 6 - FEG - AzarGrammar.com

    Chapter 6 - FEG - AzarGrammar.com

    PLURAL ADJECTIVE PLURAL PRONOUN other + -s only as a plural pronoun 6-16 LET'S PRACTICE One of our friends wants to go to the movies. _____ wants to go dancing. _____ want to stay home and play video games. Another...
  • Diapositiva 1 - gsanegr.ro

    Diapositiva 1 - gsanegr.ro

    Pintea Angela Violeta Gradul I Fizică TIC 5. Bărbuş Nadia Elena Gradul I Chimie-fizică Managementul economic 6. Miclăuş Mihai Gradul I Chimie-fizică TIC 7. Bud Rodica Nicoleta Gradul I Biologie-chimie 8. Vraja Cornelia Gradul I Biologie-chimie Protecţia mediului 9.