1. Gene Regulation
Ability of an organisms to control which genes are present in response to the environment

2. Prokaryotic cells turn genes on and off by controlling transcription
A promotor – DNA segment that allows a gene to be transcribed
An operator – part of DNA that turns a gene “on” or “off”
An operon includes promoter, operator, and genes that code for the proteins
most common in prokaryotes
The lac operon was one of the first to be discovered

3. The lac operon acts like a switch.
The lac operon is “off” when lactose is not present.
The lac operon is “on” when lactose is present.

4. Trp operon
lac operon

5. Points of control
The control of gene expression can occur at any step in the pathway from gene to functional protein
1. packing/unpacking DNA
2. transcription
3. mRNA processing
4. mRNA transport
5. translation
6. protein processing
7. protein degradation

6. 1. DNA packing as gene control
Degree of packing of DNA regulates transcription
tightly wrapped around histones
no transcription
genes turned off
heterochromatin
darker DNA (H) = tightly packed
euchromatin
lighter DNA (E) = loosely packed H E

7. DNA methylation Methylation of DNA blocks transcription factors
no transcription
 genes turned off
attachment of methyl groups (–CH3) to cytosine
nearly permanent inactivation of genes
ex. inactivated mammalian X chromosome = Barr body
Methylation results in a human disease called fragile X syndrome

8. Methylation of H19 inactivates transcription
(involved in expression of insulin like growth factor)

9. Histone acetylation Acetylation of histones unwinds DNA
loosely wrapped around histones
enables transcription
genes turned on
attachment of acetyl groups (–COCH3) to histones
conformational change in histone proteins
transcription factors have easier access to genes

10. Fig a
Chromatin remodeling
Acetylation of histones enhances access to promoter region and facilitates transcription.

11. Epigenetic Inheritance
Although the chromatin modifications just discussed do not alter DNA sequence, they may be passed to future generations of cells
The inheritance of traits transmitted by mechanisms not directly involving the nucleotide sequence is called epigenetic inheritance

12. 2. Transcription initiation
Control regions on DNA
promoter
nearby control sequence on DNA
binding of RNA polymerase & transcription factors
“base” rate of transcription
enhancer
distant control sequences on DNA binds activator proteins
“enhanced” rate of transcription
Silencer proteins- bind to enhancer sequence & block gene transcription

13. Model for Enhancer action
Much of molecular biology research is trying to understand this: the regulation of transcription.
Silencer proteins are, in essence, blocking the positive effect of activator proteins, preventing high level of transcription.

14. 3. Post-transcriptional control
Alternative RNA splicing
variable processing of exons creates a family of proteins

15. Regulation by alternative splicing
Calcitonin gene-related peptide

16. 4. Regulation of mRNA degradation
Life span of mRNA determines amount of protein synthesis
mRNA can last from hours to weeks

17. 5. Control of translation
Block initiation of translation stage
regulatory proteins attach to 5' end of mRNA
prevent attachment of ribosomal subunits & initiator tRNA
block translation of mRNA to protein

18. 6-7. Protein processing & degradation
folding, cleaving, adding sugar groups, targeting for transport
Protein degradation
ubiquitin tagging
proteasome degradation
The cell limits the lifetimes of normal proteins by selective degradation. Many proteins, such as the cyclins involved in regulating the cell cycle, must be relatively short-lived.
Protein processing movie

19. Noncoding RNAs play multiple roles in controlling gene expression
Only a small fraction of DNA codes for proteins, rRNA, and tRNA
A significant amount of the genome may be transcribed into noncoding RNAs
Noncoding RNAs regulate gene expression at two points: mRNA translation and chromatin configuration

20. RNA interference Small interfering RNAs (siRNA)
short segments of RNA (21-28 bases)
bind to mRNA
create sections of double-stranded mRNA
“death” tag for mRNA
triggers degradation of mRNA
cause gene “silencing”
post-transcriptional control
turns off gene = no protein produced
siRNA

21. Action of siRNA siRNA mRNA degraded functionally turns gene off
dicer enzyme
mRNA for translation
siRNA
double-stranded miRNA + siRNA
breakdown enzyme
(RISC)
mRNA degraded
functionally turns gene off

22. Eukaryotic Gene Regulation
Hox genes – controls differentiation of genes
Responsible for general body pattern of most animals
Order of genes is order of body parts