Transcript Bio1100Ch19W

CHAPTER 19
THE ORGANIZATION AND CONTROL OF
EUKARYOTIC GENOMES
All cells contain all genes….
…yet a given cell only expresses 5% of it’s genes
How does the cell know which genes to turn on and which to turn off??
Part of the answer lies in _____________________
DNA is packaged into ___________
• Histones
• are present in all organisms
• are _______________that package DNA
• have positive charged charged amino acids bind tightly to
___________________________ charged DNA.
• give the appearance of beads on a string
• are temporarily displaced by polymerases during transcription
and replication
DNA wrapped around histones
form a _______________
Fig.19.2
• DNA is further
packed tighter and
tighter into fibers
and domains by
mostly unknown
mechanisms
Fig. 19.2
Cells in must accomplish two tasks:
• 1. Continually turn on and off certain genes in
response to signals from the environment.
• 2. Regulate expression of genes common for cell
function and specialized functions (liver vs kidney
function)
How is expression of all these genes regulated???
Many levels of
control are available
to control expression
of any given gene…
Factor affecting
transcription
Transcription rate
RNA processing
…..but most
regulation is at
the level of
_______________
RNA stability
Translation
Protein modification
Protein cleavage
Protein stability
Fig. 19.3
So how do we regulate transcription????
1. ______________________________
• Chromosomes regions that remain highly
condensed are called__________________,
•Regions less condensed are called _______________.
• Genes located in highly condensed regions are mostly not expressed
• In contrast, genes located in less condensed regions are often
expressed
2. __________________ (-CH3) groups added to
DNA bases after DNA synthesis.
• High methylation correlates with _____________DNA
CH3
CH3
AGCGTGATGATGCGCACATA
DNA
3. Histone _____________ (addition of an acetyl
group -COCH3)
Acetylated histones grip DNA less tightly, providing
easier access for transcription proteins in this region.
nucleosome
Ac
Ac
H4
H3
H2A
H2B
Ac
Ac
Increased acetylation = increased transcription
DNA
Peptide-CH-CH2-CH2-CH2-CH2-NH-C-CH3
O
Acetylation of lysine
Several ___________________can
transcription factors
acetylate or deacetylate histones
4. DNA__________________
Fig. 19.5
Specific _______________ near promoters bind specific
Fig. 19.6
transcription factors
These transcription
factors then assist in
loading ____________
on the gene by “talking”
to the transcription
initiation complex
Tissue-specific expression is due to
_____________ action of transcription factors
Example:
HNF3a
HNF4
HNF1a
C/EBP
HNF3a
Liver-specific genes
Genetics, Russell, p6.
Transcription factors
1850 (6%)
30,000 genes
320 cell types
700 Liver-specific genes
Cancer results from genetic changes that
affect the cell cycle
• Cancer - a disease in which cells escape from the
control methods that normally regulate cell growth
and division.
• ________________ - genes that can cause cancer
• Discovered in viruses
• ________________ are close counterparts of
oncogenes found in other organisms.
If overexpressed- cause uncontrolled cell growth
What can cause proto-oncogenes to over-express??
1. _____________
3. _____________
2. ____________
Fig. 19.11
Tumor-suppressor genes
These prevent cancer by repairing DNA or preventing rapid
cell division
If mutate a tumor suppressor gene- leads to ________
The Ras gene- (a protooncogene) is mutated in _____ of human
cancers
The _____ gene- (a tumor suppressor) is mutated in 50% of
human cancers
•Called the “___________________ of the genome” because:
1. It stops the cell cycle
2. It repairs damaged DNA
3. It caused the cell to _______________ if not repairable
Most cancers are due to multiple gene mutations
Fig. 19.13
Colorectal cancer
Some viruses carry oncogenes- lead to cancer
•leukemia, liver cancer, and cancer of the cervix.
Some folks are _______________ to cancer
• 15% of colorectal cancers involve inherited
mutations.
• Between 5-10% of breast cancer cases, the 2nd most
common U.S. cancer, show an __________
predisposition.
• Mutations to one of two tumor-suppressor genes,
BRCA1 and BRCA2, increases the risk of breast and
____________ cancer.
New technology- A blood test to determine if a woman
has any point mutations in her BRCA1 or BCRA2 genes