Transcript March 24th Powerpoint

Day Date Subject To be read prior to this class period:
Th
3/12
Chapter 7
T
3/17
students = epigenetics Richie
Th
3/19
students = toxicology and cancer Anna, Bouradee
T
3/24
Th
3/26
T
3/31
no class - Spring Break
Th
4/2
no class - Spring Break
T
4/7
students = life cycles
Th
4/9
Chapter 9
second short writing assignment due at the start of class on Thurs, 4/9
T
4/14
students = nutrients and development Meg, Zeb
Th
4/16
T
4/21
students = evolution Greg
Th
4/23
Chapter 10
T
4/28
Th
4/30
Capstone Papers due
Chapter 8
T
5/5
Discussion of Capstone Papers
Th
5/7
Chapter 8
Comprehensive Final Exam, Thursday, May 7th, 8:00 – 10:00 AM
1
second short writing assignment for your Capstone project:
1)Describe your career goals.
2)Describe you past, current, and future career plans and efforts.
3) Explain which college course has had the most impact on your
career plans and why (not this class).
4) Connect your career goals, plans, and efforts with your Capstone
project efforts in as many ways as you can. These can be similarities
and/or differences.
5) What kind of sources/references could be include in this writing?
Incorporate at least five sources/references.
2
epigenetics
toxicology and cancer
3
epigenetics (narrow definition) = DNA methylation and/or
histone modification
DNA methylation stories:
1) promoter of the glucocorticoid receptor
2) thrifty phenotype in mammmals
3) folic acid (methyl donor) in obesity of agouti rats
4) queen ants
5) transgenerational
6) Richie’s paper on the “methylome”
imprinting
embryonic stem cells
4
In the promoter for the glucocorticoid receptor
I Googled:
glucocorticoid receptor DNA methylation brain
6
epigenetics (narrow definition) = DNA methylation and/or
histone modification
DNA methylation stories:
1) promoter of the glucocorticoid receptor
2) thrify phenotype in mammmals
3) folic acid (methyl donor) in obesity of agouti rats
4) queen ants
5) transgenerational
6) Richie’s paper on the “methylome”
imprinting
embryonic stem cells
7
There are many examples of maladaptive responses in Chapter 7
plus new examples that aren’t maladaptive.
maladaptive = a misinterpretation of the environment
Dutch Hunger Winter
8
There are many examples of maladaptive responses in Chapter 7
plus new examples that aren’t maladaptive.
maladaptive = a misinterpretation of the environment
Dutch Hunger Winter
The thrifty phenotype hypothesis is a example of a
Predictive Adaptive Response.
All the examples from the first third of the course were PARs.
9
There are many examples of maladaptive responses in Chapter 7
plus new examples that aren’t maladaptive.
maladaptive = a misinterpretation of the environment
Dutch Hunger Winter
10
correlation of adult blood pressure and birth rate:
11
Molecular mechanism might be in the kidney?
12
thrifty phenotype in mammals
KIDNEY:
Poor nutrition during fetal life reduces the number of
nephrons predisposing the person to high blood
pressure later in life.
PANCREAS:
Poor nutrition during fetal life reduces the number of
insulin-secreting cells predisposing the person to type 2
diabetes later in life.
LIVER:
Poor nutrition during fetal life changes histology and
gene expression of the liver. One result is that more
glucose is made and less is degraded.
13
Thrifty Phenotype Hypothesis:
Malnourished fetuses are “programmed” to expect poor nutrients postnatally
and set their biochemical parameters to conserve energy and store fat.
14
15
Thrifty Phenotype Hypothesis:
Malnourished fetuses are “programmed” to expect poor nutrients postnatally
and set their biochemical parameters to conserve energy and store fat.
The thrifty phenotype appears to be triggered by either poor nutrients or
stress. (???)
16
epigenetics (narrow definition) = DNA methylation and/or
histone modification
DNA methylation stories:
1) promoter of the glucocorticoid receptor
2) thrifty phenotype in mammmals
3) folic acid (methyl donor) in obesity of agouti rats
4) queen ants
5) transgenerational
6) Richie’s paper on the “methylome”
imprinting
embryonic stem cells
17
Environment can affect phenotype.
Environment = nutrients = folic acid (a methyl donor)
Phenotype = fur color and obesity
Plasticity caused by = methylation patterns of the agouti gene
Reaction Norm
epigenetics (narrow definition) = DNA methylation and/or
histone modification
DNA methylation stories:
1) promoter of the glucocorticoid receptor
2) thrifty phenotype in mammmals
3) folic acid (methyl donor) in obesity of agouti rats
4) queen ants
5) transgenerational
6) Richie’s paper on the “methylome”
imprinting
embryonic stem cells
19
EXPERIMENT:
When fed methylation inhibitors, larvae develop into queens.
The environment (nutrients in the form of ‘royal jelly’) acts to
increase hormones (juvenile hormone + insulin signaling) and their
effects include decreased DNA methylation, which increases
expression of genes needed to form queens.
20
epigenetics (narrow definition) = DNA methylation and/or
histone modification
DNA methylation stories:
1) promoter of the glucocorticoid receptor
2) thrifty phenotype in mammmals
3) folic acid (methyl donor) in obesity of agouti rats
4) queen ants
5) transgenerational
6) Richie’s paper on the “methylome”
imprinting
embryonic stem cells
21
Definition from Genetics:
allele = one version of a gene.
chromatin = DNA plus associated proteins. Chromosomes are
composed of chromatin.
Looking ahead to Chapter 10:
Altered chromatin can be inherited and is called an epiallele.
22
We have had examples of maladaptive responses that involve
DNA methylation:
Pregnant rats fed a low-protein diet have offspring
predisposed to obesity. In Chapter 7, there
are changes in DNA methylation on the PPARalpha
and Dnmt1 genes (involved in fat production).
Transgenerational
Multigenerational
epigenetics (narrow definition) = DNA methylation and/or
histone modification
DNA methylation stories:
1) promoter of the glucocorticoid receptor
2) thrifty phenotype in mammmals
3) folic acid (methyl donor) in obesity of agouti rats
4) queen ants
5) transgenerational
6) Richie’s paper on the “methylome”
imprinting
embryonic stem cells
24
research article Richie selected
25
26
28
29
11.5 germ cell migration
In primordial germ cells (PGCs) representing the precursors
of SSCs and all other germ cells, the genome is demethylated
and, in particular, the genomic imprints, i.e. the parent-specific methylation
marks of imprinted genes, of the previous generation are erased
from the grandparental chromosomes (with respect to the new
embryo). In the mouse, this wave of genome-wide epigenetic reprogramming
starts between day 10.5 post conceptionem (p.c.) before
migration of PGCs into the genital ridge and is completed by day 13.5
p.c. (Hajkova et al., 2002; Yamazaki et al., 2003). In the male germline,
the establishment of novel methylation marks for imprinted genes begins
around day 15.5 p.c., but is finished only after birth (Davis et al., 1999,
2000; Li et al., 2004). After fertilization, a second wave of genome-wide
epigenetic reprogramming takes place in which the vast majority of male
and female germline-derived methylation patterns are erased again and
new somatic methylation patterns for development of the new organism
are established (Mayer et al., 2000a, b). To the extent of present knowledge,
imprinted genes escape this second wave and maintain their
germline-specific methylation and parent-specific expression patterns
throughout further development (Morgan et al., 2005). Thus, imprinted
genes display a differential methylation of their parental alleles and maintenance
of genomic imprinting in both ESCs and somatic cells. In contrast,
pluripotency marker genes such as Oct4 and Nanog switch from
a transcriptionally active and demethylated state in ESCs to a transcriptionally
repressed and fully methylated state in somatic cells (Okita et al.,
2007; Wernig et al., 2007).
32
In primordial germ cells (PGCs) representing the precursors
of SSCs and all other germ cells, the genome is demethylated
and, in particular, the genomic imprints, i.e. the parent-specific methylation
marks of imprinted genes, of the previous generation are erased
from the grandparental chromosomes (with respect to the new
embryo).
33
In primordial germ cells (PGCs) representing the precursors
of SSCs and all other germ cells, the genome is demethylated
and, in particular, the genomic imprints, i.e. the parent-specific methylation
marks of imprinted genes, of the previous generation are erased
from the grandparental chromosomes (with respect to the new
embryo). In the mouse, this wave of genome-wide epigenetic reprogramming
starts between day 10.5 post conceptionem (p.c.) before
migration of PGCs into the genital ridge and is completed by day 13.5
p.c. (Hajkova et al., 2002; Yamazaki et al., 2003).
34
In primordial germ cells (PGCs) representing the precursors
of SSCs and all other germ cells, the genome is demethylated
and, in particular, the genomic imprints, i.e. the parent-specific methylation
marks of imprinted genes, of the previous generation are erased
from the grandparental chromosomes (with respect to the new
embryo). In the mouse, this wave of genome-wide epigenetic reprogramming
starts between day 10.5 post conceptionem (p.c.) before
migration of PGCs into the genital ridge and is completed by day 13.5
p.c. (Hajkova et al., 2002; Yamazaki et al., 2003). In the male germline,
the establishment of novel methylation marks for imprinted genes begins
around day 15.5 p.c., but is finished only after birth (Davis et al., 1999,
2000; Li et al., 2004). After fertilization, a second wave of genome-wide
epigenetic reprogramming takes place in which the vast majority of male
and female germline-derived methylation patterns are erased again and
new somatic methylation patterns for development of the new organism
are established (Mayer et al., 2000a, b). To the extent of present knowledge,
imprinted genes escape this second wave and maintain their
germline-specific methylation and parent-specific expression patterns
throughout further development (Morgan et al., 2005). Thus, imprinted
genes display a differential methylation of their parental alleles and maintenance
of genomic imprinting in both ESCs and somatic cells. In contrast,
pluripotency marker genes such as Oct4 and Nanog switch from
a transcriptionally active and demethylated state in ESCs to a transcriptionally
repressed and fully methylated state in somatic cells (Okita et al.,
2007; Wernig et al., 2007).
35
In primordial germ cells (PGCs) representing the precursors
of SSCs and all other germ cells, the genome is demethylated
and, in particular, the genomic imprints, i.e. the parent-specific methylation
marks of imprinted genes, of the previous generation are erased
from the grandparental chromosomes (with respect to the new
embryo). In the mouse, this wave of genome-wide epigenetic reprogramming
starts between day 10.5 post conceptionem (p.c.) before
migration of PGCs into the genital ridge and is completed by day 13.5
p.c. (Hajkova et al., 2002; Yamazaki et al., 2003). In the male germline,
the establishment of novel methylation marks for imprinted genes begins
around day 15.5 p.c., but is finished only after birth (Davis et al., 1999,
2000; Li et al., 2004). After fertilization, a second wave of genome-wide
epigenetic reprogramming takes place in which the vast majority of male
and female germline-derived methylation patterns are erased again and
new somatic methylation patterns for development of the new organism
are established (Mayer et al., 2000a, b). To the extent of present knowledge,
imprinted genes escape this second wave and maintain their
germline-specific methylation and parent-specific expression patterns
throughout further development (Morgan et al., 2005). Thus, imprinted
genes display a differential methylation of their parental alleles and maintenance
of genomic imprinting in both ESCs and somatic cells. In contrast,
pluripotency marker genes such as Oct4 and Nanog switch from
a transcriptionally active and demethylated state in ESCs to a transcriptionally
repressed and fully methylated state in somatic cells (Okita et al.,
2007; Wernig et al., 2007).
36