acetylation.html: 18_07HistoneTails-L.jpg
Chromatin modification: histone acetylation.
Enzymes can add
negative acetyl groups (—COCH3)
to positively charged lysines in histone
tails.
This process loosens chromatin structure,
making the DNA accessible to transcription.
Such chromatin modifications may be passed to future generations of cells
in a process called epigenetic inheritance.
activator.html: 18_09ActivatorAction_3-L.jpg
Activator proteins bind to distal control elements grouped as an enhancer in the DNA.
A DNA-bending protein brings the bound activators closer to the promoter.
The activators bind to transcription factors and mediator proteins, forming
a transcription initiation complex on the promoter with RNA polymerase.
Other transcription factors function as repressors.
bicoid.html: 18_19cDrosBicoidGene-L.jpg
Gradients of bicoid mRNA and bicoid protein in egg and early embryo
leads to normal
development of the head.
Continue
bicoid2.html: 18_19aDrosBicoidGene-L.jpg
A lethal mutation in the mother’s bicoid gene leads to tail structures at both ends in the
Drosophila mutant
embryo.
colorectal_1.html: 18_22bCancerDevelopment-L.jpg
Mutations affecting tumor–suppressor genes (such as p53)
may lead to benign growth in the colon lining called a polyp.
colorectal_2.html: 18_22cCancerDevelopment-L.jpg
Mutations in other tumor–suppressor genes and development of oncogenes
can cause enlargement of the benign growth into an adenoma.
Next
colorectal_3.html: 18_22dCancerDevelopment-L.jpg
Continured accumulation of mutations can culminate in the development of full-fledged cancer.
This malignant tumor is called a carcinoma.
colorectal_cancer.html: 18_22aCancerDevelopment-L.jpg
A multistep model for the development of colorectal cancer.
Affecting the colon and/or rectum, this type of cancer is one of the best understood.
Next
control_elements.html: 18_08EukGeneTranscript_3-L.jpg
Transcription control.
Distal control elements (far from the promoter, where RNA polymerase binds,)
can be grouped together as enhancers and may interact with
activators
or repressors to control initiation of transcription.
cytoplasmic.html: 18_15aEarlyEmbryoDevinfo-L.jpg
Cytoplasmic determinants.
Uneven distribution
of determinants, such as RNA, proteins, and organelles,
in the cytoplasm of the unfertilized egg
affect expression of genes and ultimately the cell’s developmental fate.
cytoplasmic_Drosophila.html: 18_17bDrosophilaDevelop-L.jpg
Cytoplasmic determinants
such as mRNA establish the axes of the body in Drosophila.
Asymmetrically distribution of these molecules in the unfertilized egg
eventually lead to differentiation of specialized segments of the
adult.
One important egg-polarity gene that encodes for such mRNA is the
bicoid gene.
determination.html: 18_16DetermDifferentiat_3-L.jpg
Cell determination.
MyoD is a “master regulatory gene”
that produce proteins that commit the cell to becoming skeletal muscle.
If a myoblast
cell produces the MyoD protein (a transcription factor),
it binds to enhancers
of many target genes.
The cell is now determined to be a skeletal muscle cell.
differentiation.html: 18_06-EukGeneExpRegulatio-L.jpg
Differences between cells is mainly due to differential gene expression,
even though different cells share genomic equivalence.
euk-regulation_cytoplasm.html: 18_06bEukGeneExpRegulatio-L.jpg
In the cytoplasm, regulation can occur by
euk-regulation_nucleus.html: 18_06aEukGeneExpRegulatio-L.jpg
Regulation of eukaryotic gene expression may take place at different stages.
In the nucleus, regulation can occur by
expression.html: 18_10CellSpecificTranscri-L.jpg
The control elements can activate transcription only when the appropriate
activator proteins are present.
The particular combination of control elements and activator proteins
enables a liver cell to express the albumin gene,
while a lens cell expresses the crystallin gene.
homeotic.html: 18_18-AbnormalPatternForm-L.jpg
Mutations in homeotic genes cause a misplacement of structures in an animal.
An homeotic mutant Drosophila bears a pair of legs in place of antennae.
induction.html: 18_15bEarlyEmbryoDevinfo-L.jpg
Induction by nearby cells.
The cells at the bottom of this early embryo release
chemicals that signal nearby cells to change their gene expression (transcription).
lac_CAP.html: 18_23LacOperonCAPA.jpg
Lactose present, glucose scarce (cAMP level high): lac transcription stimulated.
RNA polymerase has high affinity for the lac promoter only when the activator, catabolite-activating protein
(CAP), is bound next to the promoter.
CAP is active only when associated with cyclic AMP
(cAMP),
whose concentration in the cell rises when the concentration of the preferred glucose falls.
lac_inactive.html: 18_23LacOperonCAPB.jpg
Lactose present, glucose abundant (cAMP level low): lac transcription reduced.
When glucose levels increase, cAMP levels drop, and
the catabolite-activating protein (CAP) is inactive.
The cell preferentially catabolizes glucose and does not make the lactose–utilizing enzymes.
lac_induced.html: 18_22bLacOperon.jpg
Lactose present, repressor inactive, operon on.
Allolactose
, an isomer
of lactose, serves as an inducer
and derepresses the operon by inactivating the repressor,
turning on transcription and translation of enzymes for lactose digestion.
lac_operon.html: 18_22aLacOperon.jpg
Lactose absent, repressor active, operon off.
E. coli uses 3 enzymes to take up and metabolize the sugar lactose
.
The genes for these 3 enzymes are clustered in the lac operon.
In the absence of lactose
,
a repressor switches off the operon by binding to the operator.
mRNA_degradation.html: 18_13miRNAsAndGeneExp-L.jpg
mRNA degradation.
morphogenesis.html: 18_14-FertEggToAnimal-L.jpg
Morphogenesis encompasses the processes that give shape to the organism and its parts.
It takes just one week for cell division, differentiation,
and morphogenesis to transform a fertilized frog egg into a hatching tadpole.
p53_tumor-suppressor.html: 18_21bCellCycleReg-L.jpg
The p53 tumor suppressor gene encodes a transcription factor that
regulates transcription of more than 50 different genes involved in the cell
cycle.
Cells with mutant p53 are unable to arrest at cell cycle checkpoints and become cancerous.
_Vid_Discover2e/ch11a04_p53-tumor-suppressor.swf
proteasome.html: 18_12ProteasomeActivity-L.jpg
Protein degradation.
Unneeded proteins can be tagged with the protein ubiquitin.
The tagged protein is then chopped up by a proteasome.
proto-oncogene.html: 18_20OncogeneMutation-L.jpg
Proto-oncogenes are normal genes involved in cell growth and division.
Mutations to a proto-oncogene can lead it to become a cancer-causing oncogene
by producing growth-stimulating proteins
that are in excess
levels or that are hyperactive
or degradation
-
resistant
.
splicing.html: 18_11AltRNASplicing-L.jpg
RNA processing: alternative RNA splicing.
The primary transcripts of some genes can be spliced in more than one way,
generating different mRNA molecules.
In this example one mRNA molecule has ended up with the green exon
and the other with the purple exon.
With alternative splicing,
an organism can produce more than one type of polypeptide from a single gene.
trp_operon.html: 18_21aTrpOperon_L.jpg
Tryptophan absent, repressor inactive, operon on.
In the repressible trp operon,
5 genes encoding the enzymes to synthesize tryptophan (an amino acid) are regulated by a
promoter and an operator.
When tryptophan is absent,
the repressor (controlled by its own promoter)
is inactive
and the operon is on
.
RNA polymerase attaches to the DNA at the promoter and transcribes the operon’s genes.
trp_regulation.html: 18_02MetabolicPathwayReg-L.jpg
An operon is
a group of functionally related genes under the control by a single on-off “switch”
called an operator which is usually located within the promoter.
Enzyme activity can be controlled by
trp_repressed.html: 18_21bTrpOperon_2.jpg
Tryptophan present, repressor active, operon off.
The presence of tryptophan (a corepressor) activates
the repressor
which binds to the operator to turn the operon off
by
inhibiting the transcription of these genes by RNA polymerase.