Gene Regulation

I. Introduction

• cell contains a lot of DNA, but not all of it is needed all of the time

-transcriptional level (RNA polymerase, promoter)

-post-transcriptional regulation

-post-translational regulation

• prokaryotes (simpler system) and eukaryotes (more complex)

II. Gene Regulation in Prokaryotes

A. Types of genes: 

E. coli - 4403 genes (1997)

    - housekeeping

    - inducible (turn on) or repressible (turn off)

B. Operon Theory

How are inducible genes regulated?

• Jacob, Monod, Lwoff  Nobel prize 1965
• How do bacteria utilize lactose? (e.g. sugar in milk)-need to produce three enzymes
• lactose --> galactose + glucose (ß-galactosidase)
• What is an operon?

The lactose (lac) operon animation (inducible)

• What is the promoter?
• What is the operator?
• What determines if the operator is on or off?
• What controls RP binding?
• How does the concentration of lactose regulate the operon?

• Tryptophan is an essential amino acid that is always needed by the bacterial cell. 
• structural genes in 'tryp' operon code for synthetic enzymes that make tryptophan 
• Operon is always "on"
• the operon can be turned off (repressed) if tryptophan concentration in the growth medium is high
• The tryptophan operon(animation)  animation2
• What is the corepressor?

III. Gene Regulation in Eukaryotes

A. Types of genes

-more information (~30,000 genes/human nucleus)

-three types:

a. housekeeping (always expressed)

b. as needed for growth and differentiation

c. expressed in response to environmental change

How are eukaryotic genes regulated?

equivalent of an operon in eukaryotes is the gene control region:

-contains structural gene (exon), promoter site, regulatory binding sites

-much larger than operon (50,000 b.p. in length)

-gene regulatory proteins (GRP's) are far more numerous (5-10% of genome codes for them) than bacterial RP's-may be enhancers, repressors or silencers (as needed)

B. Some aspects of eukaryotic gene regulation

1. Example of how GRP's can change the rate of transcription

promoters in DNA: basal promoter (TATA), plus binding site for RNA polymerase

      [there are also upstream promoters called UPE's (upstream promoter elements)]

TF's (transcription factors) bind to basal promoter; may form a loop with enhancer to increase transcription rate

loop complex of GRP, TF, RNA polymerase (bound to promoter) called the 'enhancesome'

3. Relationship between gene activity and chromosome structure

heterochromatin (inactive genes)

euchromatin (active genes)

role of chromatin modifying enzymes (chromatin remodeling complex-opens up nucleosomes)

Lampbrush chromosomes diagram

chromosomal 'puffs' in polytene chromosomes of Drosophilia

Barr bodies 

Barr Body-permanently heterochromatinized X chromosome

from: http://www.mdarchives.state.md.us/msa/mdmanual/01glance/symbols/html/cat.html

Calico Cat always females

heterozygous for black and orange hair:  X^BX^b  (X^B=black)  (X^b=orange)

randomly inactivated during embryo development example

What color will male cats exhibit?

anhidrotic ectodermal dysplasia

4. post-transcriptional modification

Exon shuffling (essential regulatory point for expression of genetic information)

covalent modification of mRNA (polyA tail is a 'timer' determining life span of mRNA)

post-translational regulation (environmental conditions influence protein shape/activity; molecular chaperones) video