epigenetics-foetal programming.ppt.........

Epigenetics feotal programming

2. Epigenetics

3. Barkers Hypothesis:

The ‘fetal origins’ or ‘Barker’ hypothesis
suggests that impaired growth of the
fetus during gestation strongly
correlates to the development of
chronic disease in later life.

4. Some Examples
Size at birth is related to experience of disease and poorer
long-term health outcomes in later life

Another example is smoking during pregnancy which not
only influences weight at birth but can also increase the
likelihood of miscarriage and the development of childhood
asthma
Foetal alcohol syndrome is a developmental disorder that
can occur after heavy alcohol use by pregnant women’. FAS
can cause a range of problems including growth (pre and
post natal), abnormal facial features, mental disability and
behavioural problems.

5. Programming Effects
•role of epigenetics

•nuclear receptors
• reactive oxygen species (ROS)
•and markers of endoplasmic reticulum stress
(ERS).

6. Epigenetic patterns of gene expression
are thus largely established in utero
•Histone de-acetylation and promoter
methylation are among the regular
mechanisms by which the fate of developing
cell lines is determined
•Once established in a given tissue, the
patterns of histone acetylation and promoter
methylation are usually not altered during the
life of an organism

7. DNA methylation
DNA methylation, via the addition of a methyl group to CpG sites on the DNA by
members of the DNA methyltransferase family.
A high fat diet throughout pregnancy and lactation lead to alterations in methyl CpG
binding protein-2, a protein involved in the silencing of genes via DNA methylation
 Another study in baboon offspring of maternal nutrient restricted mothers found
altered patterns of global DNA methylation in the brain, liver, and kidney between
nutrient restricted offspring and offspring whose mothers received adequate food
intake
 In humans, trial examining the effects of micronutrient supplementation during the
pre- and periconceptual period found different methylation patterns at differentially
methylated regions between the supplement group and the placebo group.
 The current evidence suggests that DNA methylation may be a
key player in modulating phenotypes in response to the
environment.

8. Post-translational histone modifications
“Histone code”
•Methylation
• acetylation
• phosphorylation
• ubiquitination and
•ADP-ribosylation of histones
histone acetylases and methyltransferases

9. •Understanding how maternal nutritional
status alters the activity of the fetal enzymes
mediating histone de-acetylation and
promoter methylation may yield insights into
ways in which enzyme activity might be
buffered from maternal condition
•Alternatively, it may be possible to reverse
deleterious epigenetic patterns after birth.

10. Epigenetics Mechanisms
Gene Expression
RNA Interference
Histone Modifications
DNA Methylation

14. DNA methylation is important in:
Transcriptional gene silencing
Maintain genome stability
Embryonic development
Genomic imprinting
X chromosome inactivation
(females)

15. DNA Methylation
http://www.cellscience.com/reviews7/Taylor1.jpg
Hypomethylation
Hypermethylation

16. Chromatin- Euchromatin + heterochromatin
heterochromatin
Euchromatin

17. Unique Sequences : 30-75%
•single-copy gene
• Highly Repetitive Sequences : 5-45%
* typically 50-300 bp / repeat;
* >105 copies / genome
•Alu repeat; SINE, LINE retrotransposon
• Middle-Repetitive Sequences: 1-30%
* 10-1000 copies / genome
* Histone, tRNA genes / 20-600 copies
* P-element, copia transposon/ 10-50 copies
Unique and Repetitive Sequences in Eukaryotic Genomes

18. 10-69
The alignment of sister chromatids via cohesinFigure 10.24
Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display
Cohesins along
chromosome arms are
released
Cohesin
remains at
centromere
Cohesin at
centromer is
degraded

19. 10-68
The condensation of a metaphase chromosome by condensinFigure 10.23
Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display
The number of loops has not changed
However, the diameter of each loop is smaller
Condesin travels
into the nucleus
Condesin binds to
chromosomes and
compacts the
radial loops
During interphase,
condensin is in the
cytoplasm