Epigenesis and

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Epigenesisand Genetic Regulation
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Mechanisms of Gene Expression
1) X chromosome inactivation (Lyonization)
2) Genomic Imprinting
3) RNA Splicing
4) Photocopy (Transcriptional) Regulation
4.a) Methylation
4.b) Transcription Factors
5) Packaging (Post-Translational) Regulation
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X Chromosome Inactivation (Lyonization)

• At fertilization, both X chromosomes are active.
• Very soon, however, one of the X chromosomes in a
  cell, apparently taken at random, is inactivated
  and forms a Barr body.
• All other cells derived from the initial cell
  have the SAME X chromosome inactivated.
• Genes on the inactive X chromosome are not
  expressed.
• In humans, though, a few genes are expressed.

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Barr Bodies
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Mechanism

• XIST gene on the X chromosome turns on and
  produces XIST RNA.
• Molecules of XIST RNA accumulate along the
  chromosome with the active XIST gene.
• The binding of the XIST RNA with the DNA turns
  off the genes on that chromosome.

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RNA Splicing
Polypeptide 1
Polypeptide 2
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snRNP (snurps) small nuclear ribonucleoprotein
particles
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RNA Splicing

• Varies among species.
• Possible reason why number of human genes is so
  small.
• Example Amyloid Precursor Protein (APP) gene.
• Might be very common in the human brain.

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Genomic Imprinting

• Some genes are turned off when inherited from
  the father and turned on when inherited from the
  mother.
• Other genes are turned on when inherited from
  father but turned off when inherited from
  mother.
• Mechanisms methylation phosphorylation of
  histones.

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Transcriptional RegulationI Methylation

• Methyl group (CH3) added to DNA
• Shuts off genes (prevents transcription)
• Tissue specific (e.g., genes methylated in the
  MHC differ in different tissues)
• Human Epigenome Project (map the methylated DNA
  areas in the human genome)

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Transcriptional RegulationII Transcription
Factors
Transcription factor (regulatory protein)
protein or protein complex that enhances or
inhibits transcription.
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(a) LAC Operon Turned Off
(b) LAC Operon Turned On
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Rolling winds send a tree trunk and debris your
way. Thankfully, your stress system helps you
cope. The brain's hypothalamus releases the
hormone corticotrophin-releasing factor (CRF) and
its effects make your guard go up. CRF travels to
the pituitary gland and triggers the release of
adrenocorticotropic hormone (ACTH). This hormone
travels in the blood to the adrenal glands and
instructs them to release a third hormone,
cortisol. The hormones rally the body systems and
provide energy to help you deal with the
stressful situation. You quickly flee. Perpetual
or severe stress, however, may upset the stress
system and harm the brain.
http//web.sfn.org/content/Publications/BrainBrief
ings/stress.html
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http//www.amtamassage.org/journal/su_00_journal/i
mages/body2.jpg
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CREB Transcription factor in neurons
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Posttranslational ModificationProtein
Activation/Deactivation

• Phosphorylation (add a phoshate group)
• Acetylation (add an acetyl group)
• Alkylation (add a ethyl, methyl group)
• Ubiquitination (add the protein ubiquitin to an
  existing protein usually instructs the cellular
  machinery to degrade/destroy the protein)

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Epigenesis and Development
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Homeobox Genes
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Homeobox Hox Genes(Drosophila and Mus)
http//www.people.virginia.edu/rjh9u/homeo.html
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Homeobox Hox Genes(Drossophila, Mus Homo)
http//universe-review.ca/F10-multicell.htm
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Development(Drosophila and Homo)
http//universe-review.ca/F10-multicell.htm
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Hox Genes, which control the development of the
central nervous system and the body, are common
to most organisms. Four groups of similar Hox
Genes, shown in color, appear to control related
regions of the human body and the fly. Each box
represents a single Hox Gene.
http//web.sfn.org/content/Publications/BrainBrief
ings/hox_genes.html
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Mammalian Sexual Development
1) Typical Course Female
2) Males Masculinized Females
2.a) 7th week SRY gene
2.b) testes development
2.c) large amounts of androgens ? masculinization
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http//www.ncbi.nlm.nih.gov/disease/SRY.html
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Examples of genetic regulation and epigenesis
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Neurotrophic Factors
A family of proteins produced invarious tissues
that guide the growth, migration, development and
survival of neurons and repair the processes
(e.g., dendrites) of damaged neurons
A neuron or support cell (e.g., the astrocyte)
releases the neurotrophic factor which binds to a
receptor. The binding initiates a signal that
regulates gene transcription. The protein
products then influence the growth, etc. of the
neuron. It may, for example, cause a process of
the neuron to grow in the direction of the signal.
http//web.sfn.org/content/Publications/BrainBrief
ings/ neurotrophic.htmlfullsize
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Axons locate their target tissues by using
chemical attractants (blue) and repellants
(orange) located around or on the surface of
guide cells. Left An axon begins to grow toward
target tissue. Guide cells 1 and 3 secrete
attractants that cause the axon to grow toward
them, while guide cell 2 secretes a repellant.
Surfaces of guide cells and target tissues also
display attractant molecules (blue) and repellant
molecules (orange). Right A day later, the axon
has grown around only guide cells 1 and 3.
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As the brain develops, neurons migrate from the
inner surface to form the outer layers. Left
Immature neurons use fibers from cells called
glia as highways to carry them to their
destinations. Right A single neuron, shown about
2,500 times its actual size, moves on a glial
fiber.
http//web.sfn.org/content/Publications/ BrainBrie
fings/neuron.html
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Experience influences the brain
If bigger brain parts mean a bigger intellect,
musicians may have a leg up on others. Brain
imaging research shows that several brain areas
are larger in adult musicians than in
nonmusicians. For example, the primary motor
cortex and the cerebellum, which are involved in
movement and coordination, are bigger in adult
musicians than in people who don't play musical
instruments. The area that connects the two sides
of the brain, the corpus callosum, is also larger
in adult musicians.
http//web.sfn.org/content/Publications/BrainBrief
ings/music_training_and_brain.htm
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Chronic administration of morphine in rats
shrinks dopamine neurons in the reward circuit.
The receiving branches, called dendrites, wither
and the filaments that transport important
substances down the neuron's axon are reduced.
Nerve growth factors appear to reverse the
damage.
http//web.sfn.org/content/Publications/BrainBrief
ings/addiction.html
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In the brain, certain cells can release
glutamate. This chemical can then activate
molecular complexes, including the AMPA receptor
and NMDA receptor, on nearby brain cells and
create reactions that aid memory, according to
studies. Another molecule, the GABA B receptor,
appears to suppress the process. A number of
researchers are developing and testing compounds
that target components of this system in an
effort to create medicines that can enhance
memory and thinking.
http//web.sfn.org/content/Publications/BrainBrief
ings/mem_enhance.html
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Comparative Genomics

• Tracing similarities/differences in human genes
  and genes of other mammals.
• Nascent discipline because genome of our closest
  relative (chimp) sequenced in 9/2005.
• Preliminary results suggest that a number of
  differences may be due to genes coding for
  transcription factors.
• E.g., FOXP2 may influence language