1. CPET had yet to receive any Spruce Creek applications for their programs. I’m told there are several applications that went in recently. CPET wants us to know that they have funding for about 30 scholarships and that the lack of funding should not be a reason to fail to apply. SSTP is only for rising Seniors but there is a new 2 week program in biomedical science for rising Juniors.

2. Can genes be turned on and off in cells?
Each cell expresses, or turns on, only a fraction of its genes. The rest of the genes are repressed, or turned off. The process of turning genes on and off is known as gene regulation. Gene regulation is an important part of normal development. Genes are turned on and off in different patterns during development to make a brain cell look and act different from a liver cell or a muscle cell, for example. Gene regulation also allows cells to react quickly to changes in their environments. Although we know that the regulation of genes is critical for life, this complex process is not yet fully understood.
Gene regulation can occur at any point during gene expression, but most commonly occurs at the level of transcription (when the information in a gene’s DNA is transferred to mRNA). Signals from the environment or from other cells activate proteins called transcription factors. These proteins bind to regulatory regions of a gene and increase or decrease the level of transcription. By controlling the level of transcription, this process can determine the amount of protein product that is made by a gene at any given time.
Genetics Home Reference

3. Chapter 18 Eukaryotic Gene Regulation
NUCLEUS
Chromatin
Chromatin modification
Complex
It’s not just about turning a gene on or off
The amount of protein product is regulated
Production of the protein must be coordinated with multiple inputs
Regulation varies greatly in different cell types and is responsible for maintaining specific cell types
Regulation can occur at any location on the pathway
DNA
Gene available
for transcription
Gene
Transcription
RNA
Exon
Primary transcript
Intron
RNA processing
Tail
Cap
mRNA in nucleus
Transport to cytoplasm
CYTOPLASM
mRNA in cytoplasm
Degradation
of mRNA
Translation
Polypeptide
Protein processing
Active protein
Degradation
of protein
Transport to cellular
destination
Activity: Control of Gene Expression
Cellular function

4. State of Chromatin Can Impact Gene Expression
Histones undergo chemical modifications that change chromatin organization
euchromatin - loosely packed chromatin – most of the time except mitosis & meiosis
The transcription machinery can readily access and express these genes
heterochromatin - a few regions of chromatin (centromeres and telomeres) always condensed
Difficult for the cell to express genetic information in these regions
Regulation at this level:
…tends to be long-term. A skin cell may permanently shut down expression of genes only needed in neurons
…tends to involve a large region of DNA, often encompassing more than one gene
Copyright © 2008 Pearson Education Inc., publishing as Pearson Benjamin Cummings

5. Histone H1 is one of the five main histone protein families which are components of chromatin in eukaryotic cells. Though highly conserved, it is nevertheless the most variable histone in sequence across species.

6. Chromatin Can be Modulated by Histone Modifications
Adding methyl groups - methylation – condenses chromatin – blocks gene expression
Acetylation of histone tails promotes loose chromatin structure that permits transcription
Chromatin Can be Modulated by Histone Modifications
Histone
tails
Amino
acids
available
for chemical
modification
DNA
double helix
(a) Histone tails protrude outward from a
nucleosome

7. Gene Expression Can be Controlled by Transcription Initiation
If transcription never begins, the protein is never made.
Conversely, if RNA pol is strongly attracted to the promoter, more transcript will be produced.
This sort of regulation can be accomplished in many ways

8. Gene Expression Can be Controlled by Transcription Initiation
Chromatin-modifying enzymes may close or open DNA near the promoter to transcription machinery.
Transcription Factors - RNA pol helpers that bind near the promoter (proximal control elements.) Usually, this assist RNA pol in binding the promoter, therefore they are activators.
Enhancers – Proteins that bind far from the promoter and influence it’s activity (distal control elements). These may increase or decrease transcription.
Activity: Control of Transcription

9. Gene Expression Can be Controlled by Transcription Initiation
Promoter
Activators
Gene
DNA
Distal control
element
Enhancer
TATA
box
RNA polymerase binding site
The TATA box (Goldberg-Hogness box) is a DNA sequence in the promoter region a that is bound by transcription factors. RNA polyermase recognizes this collection of transcription factors and binds.
Why have a TATA box?
Why doesn’t RNA polymerase bind directly to a promoter sequence without helpers? Or does it?
Figure 18.9 A model for the action of enhancers and transcription activators
Fig

10. Gene Expression Can be Controlled by Transcription Initiation
Promoter
Activators
Gene
DNA
Distal control
element
Enhancer
TATA
box
General
transcription
factors
DNA-bending
protein
Figure 18.9 A model for the action of enhancers and transcription activators
Group of
mediator proteins
Fig

11. Gene Expression Can be Controlled by Transcription Initiation

12. Combinatorial Control of Gene Activation
Enhancer
Promoter
Albumin gene
Control
elements
specific combinations of control elements activate transcription
Crystallin gene
LIVER CELL
NUCLEUS
LENS CELL
NUCLEUS
Available
activators
Available
activators
Figure Cell type–specific transcription
Albumin gene
not expressed
Albumin gene
expressed
Crystallin gene
not expressed
Crystallin gene
expressed
(a) Liver cell
(b) Lens cell
Fig

13. Coordinately Controlled Genes
Gene Expression Can be Controlled by Transcription Initiation
Coordinately Controlled Genes
Each eukaryotic gene has is own promoter and control elements
Genes for the same process may be scattered all over the genome, but may have the same control element combination
This way when the transcription factors that turn on one of these genes are produced, all the genes in the process are transcribed.

14. Animation: mRNA Degradation
Gene Expression Can be Controlled by Transcription Initiation
mRNA Degradation
After transcription initiation and transcription of the primary transcript, gene expression can be controlled by
Leaving the mRNA stable
Quick degradation of mRNA
mRNA lifespan = amount protein made
determined by sequences in the leader and trailer (untranslated)regions
Animation: mRNA Degradation

15. Translation Initiation
Gene Expression Can be Controlled by Transcription Initiation
Translation Initiation
regulatory proteins can block initiation of translation
Bozeman gene regulation

16. Animation: Blocking Translation
Protein Processing and Degradation
After translation, protein cleavage and modification are controlled. Some proteins are stored in an inactive form because they are needed quickly. Proteins involved in wound healing, for example.
Proteasomes - giant protein complexes that degrade protein molecules. This will immediately stop the action of the protein.
Animation: Blocking Translation

17. Proteosome degrades a protein.
Proteasome
and ubiquitin
to be recycled
Ubiquitin
Proteasome
Protein to
be degraded
Ubiquitinated
protein
Protein
fragments
(peptides)
Protein entering a
proteasome
Figure Degradation of a protein by a proteasome
Fig

18. Noncoding RNAs These are RNA transcripts that regulate gene expression
MicroRNAs (miRNA)
Small, single-stranded, bind to mRNA and degrade it or block translation
Small Interfering RNAs (siRNA)
RNAi = RNA interference – RNA inhibits gene expression
Can impact heterochromatin formation and block large chromosomal regions

19. What Is a Gene? Revisiting the Question
A discrete unit of inheritance
A region of specific nucleotide sequence in a chromosome
A DNA sequence that codes for a specific polypeptide chain or RNA
Review: Control of Gene Expression
Copyright © 2008 Pearson Education Inc., publishing as Pearson Benjamin Cummings

20. Ethylene, fruit ripening and gene expression
Read: Fruit Ripening, pg. 84