Transcript Ch 11- Controlling Gene Expression

Ch 11- Controlling Gene Expression
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Activator
Adult stem cells
Alternative RNA splicing
Carcinogens
Clones
Differentiation
Embryonic stem cells
Enhancers
Gene expression
Histones
Homeoboxes
Homeotic gene
Nuclear transplantation
Nucleosome
Oncogene
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Operator
Operon
Promoter
Proto-oncogene
Regeneration
Regulatory gene
Repressor
Reproductive cloning
Signal-transduction pathway
Silencers
Therapeutic cloning
Transcription factors
Tumor-suppressor gene
X chromosome inactivation
What is gene expression?
• Process by which genetic
information flows from
genes to proteins
(genotype to phenotype)
– Interaction of proteins and DNA turn
prokaryotic genes “on” and “off”
– Genes that are turned “on”- are being
transcribed into RNA and translated
into proteins (being expressed)
– Turning a gene “on” or “off” controls
the expression of certain genes
(expressed as proteins) in a cell
Example:
• E. coli – bacteria – regulates gene expression by
environmental changes
– lac operon- when lactose is present= cell needs to produce
protein to break it down and use it
• When lactose is absent= doesn’t want to bother making the
protein to break down lactose
– Promoter- site where RNA pol attaches
– Operator- site that determines whether promoter can bind or not
to RNA pol
– Promoter + operator + genes to be transcribed = operon
– Repressor- protein that binds to operator; blocks transcription
– Regulatory gene- outside of operon; codes for repressor; always
expressed
• Repressor will only bind if certain molecules are present (fits
into repressor)
– Activators- proteins that turn operon “on” by binding to DNA
• Makes RNA pol bind more easily
Cell differentiation produces variety
• Differentiation- cells become specialized in structure and
function
– Results from selective gene expression
– Doesn’t cause change in DNA
– Ex: muscle contraction protein gene: turned on in muscle cells,
off in RBC’s
– Differentiated cells maintain genetic potential
• Plant cells can dedifferentiate and give rise to a new
plant
• Regeneration- body part can be
re-grown
Carrot cloning
Clones and cloning
• Clone- genetically identical organism
• Nuclear transplantation- nucleus of an egg
is replaced with body cell nucleus
• Cloning in the news:
– Reproductive
• Helps in research, agriculture, medicine
– Therapeutic
• Embryonic stem cells- can give rise to any
specialized body cells; immortal in a culture
Controlling gene expression in
eukaryotes
• How DNA is packaged
– Histones- small proteins; helps coil DNA
– Nucleosome- “bead” consisting of 8 histones and
DNA wound around it
– String of “beads” is then coiled, which is then coiled
on itself
– Packaging prevents RNA pol from reaching DNA
– Histones must loosen grip on certain part of DNA,
then RNA pol may bind to DNA
Example of how DNA packaging
effects gene expression:
• X-inactivation
– In female mammals, 1 X chromosome is so tightly
compacted that it is inactive, even during interphase
– Initiated early in embryonic development
– A random event
– Heterozygous females on X chromosome will express
different X-linked alleles
– Ex: tortoiseshell cat
Complex proteins control
eukaryotic transcription
• More regulatory proteins and control sequences in
eukaryotes
• Each gene has its own promoter and control sequence
• Activators are more important than repressors usually
(default is “off”)
– Except for activities that must happen continuously,
Ex: glycolysis, their default is “on”
Complex proteins control
eukaryotic transcription
• Transcription factors- regulatory proteins that turn on
eukaryotic transcription (in addition to RNA pol)
– Activators are one type that bind to enhancer DNA
sequences; sequences that regulate far from gene
– DNA bends and TF’s bind to create an area where
RNA pol can bind to
– Silencers- are sequences that repressors bind to;
stop transcription initiation
• Coordinating gene expression- eukaryotes rarely have
operons, so enhancer sequences and transcription
factors are important for the transcription of genes
Expression is also regulated by
alternative RNA splicing
• RNA can be spliced differently to yield different
polypeptides from the same gene
• Ex: sex of fruit flies
• Can also affect when mRNA molecules move
into cytoplasm
Translation and even proteins can
also be regulated
• mRNA breakdown- Determines how many proteins are
made
– In prokaryotes- mRNA breaks down quickly
– In eukaryotes can last much longer
• Initiation of translation- proteins are in place to control
the start of translation; sometimes determined by
available chemicals
• Protein activation- polypeptides are cleaved to yield
smaller active protein
• Protein breakdown- selective breakdown; response to
change in environment
Genetic Control of Embryonic
Development
• Gene expression can
determine body plan
– Concentration gradients of
mRNA and proteins determine
body layout
– Homeotic gene- master control
gene; regulates genes that
determine body plan
– Many proteins act as signals to
notify bordering cells
• Within homeotic genes
there are sequences
that are very similar
between all
eukaryotes
– Homeoboxesnucleotide
sequences that
code for part of a
protein that can
bind to the DNA of
the gene that it
regulates
• Signal transduction
– Series of molecular changes that converts a
signal on the cell surface to a response
within the cell
• Cell to cell signaling
• Uses relay of proteins to initiate transcription
Genetics behind cancers
• Oncogene- gene that causes cancer
• Proto-oncogene- normal gene that has the potential to
become an oncogene
– Many code for growth factors (stimulate cell division)
– Can become oncogenes a few ways
– Mutation, having multiple copies of gene, movement
of gene to new location with new controls
• Tumor-suppressor genesproduces proteins that prevent
uncontrolled cell division
• If there is a mutation a cell
might start to divide
excessively
• Figure 11.15B in chapter
• Oncogene proteins
and faulty tumorsuppressor proteins
can affect signal
transduction
pathways
– Oncogene protein
can be hyper active
and stimulate cell
division
– Tumor-suppressor
protein can stop
protein that inhibits
cell division from
being produced
• Cancer does not usually start from 1 mutation in a
somatic cell
– Oncogene can be activated then tumor-suppressor genes can
be inactivated (usually more than 1 is), this possibly produces a
tumor
– An accumulation of mutations in a lineage of somatic cells can
cause a malignant cell
• Avoiding carcinogens can reduce risk
– Carcinogen- factors that alter DNA and make cancerous cells
• Ex: X-rays, UV light, tobacco (chemicals),
• When something can cause a mutation in DNA it runs a risk
of affecting the cell division control system