Transcript Histone Methylation

Transcriptional - These mechanisms prevent transcription.
Posttranscriptional - These mechanisms control or regulate
mRNA after it has been produced.
Translational - These mechanisms prevent translation. They
often involve protein factors needed for translation.
Posttranslational - These mechanisms act after the protein
has been produced.
epigenetics is the study of heritable changes in
gene expression or cellular phenotype caused
by mechanisms other than changes in the
underlying DNA sequence – hence the name
epi- (Greek: επί- over, above, outer) -genetics.
It refers to functionally relevant modifications
to the genome that do not involve a change in
the nucleotide sequence. Examples of such
modifications are DNA methylation and
histone modification, both of which serve to
regulate gene expression without altering the
underlying DNA sequence. (Wikipedia)
http://www.youtube.com/watch?v=9AfBsTAQ8
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Epigenetics primer
http://www.youtube.com/watch?v=Xjq5eEslJh
w&NR=1&feature=endscreen
http://learn.genetics.utah.edu/content/epigenetics/nutri
tion/
Nutrition and epigenetics
SAM e:
http://www.mayoclinic.com/health/same/NS_patientsame
Epigentic inheritance example X inactivation
http://www.youtube.com/watch?v=mHak9EZjySs
Transcriptional
Acetylation/deacetylation of DNA
Condensation of DNA involves coiling around proteins
called histones. Acetylation is when acetyl groups (COCH3) are attached to lysines in the histone tails. This
reduces condensation and promotes transcription
because the transcription machinery has better access to
the DNA.
Biological roles of acetylation
Histone acetylation and deacetylation have
been implicated in many biological processes,
such as cell differentiation and survival,
double-strand DNA break repair, cell cycle
progression, malignant transformation, cardiac
function and remodeling, and plant
acclimation to cold stress. Also, studies have
linked the proliferative capacity of many
solid tumors to the histone acetylation status.
The loss of acetylation at Lys16 of H4 is a
common characteristic of
human cancer. Hence, HATs and HDACs have
become some of the most promising targets in
cancer therapy.
http://extremelongevity.net/2012/06/12/dnaswitches-discovered-to-decline-significantlywith-age/
Role of DNA methylation is to silence the gene:
http://www.nature.com/scitable/topicpage/therole-of-methylation-in-gene-expression-1070
Biological roles of DNA methylation
In the mammalian genome, about 70% of CpG
dinucleotides are methylated. Many of the
remaining nonmethylated CpGs are in CpG islands
typically found in functional promoter regions.
DNA methylation has long been viewed as an
epigenetic marker of gene repression
and plays important roles in heterochromatin
formation, long-term silencing of repetitive
elements, X-chromosome inactivation and in the
establishment and maintenance of
imprinted genes.
Histone Methylation
Histone methylation is a more stable
modification than
acetylation
Biological roles of histone methylation
Recent studies have implicated histone
methylation in the maintenance of embryonic
stem (ES) cells in the undifferentiated state,
arginine demethylimination in transcriptional
repression, histone lysine demethylases in
transcriptional regulation, cancer cell
proliferation and normal neuronal function,
and the loss of trimethylation at Lys20 of H4 in
human cancer. Studies have suggested
that histone demethylation and deacetylation
are tightly coupled.
http://www.youtube.com/watch?v=29doT6Hf2
MI
How methylation silences genes
Post transcriptional modification:RNA processing.
Addition of polyAAA tail and 5-methyl gunaosine cap.
Failure to do this results in rapid degradation of the pre mRNA
http://www.youtube.com/watch?v=YjWuVrzvZ
YA
mRNA processing
Post transcriptional modification:RNA modification: exons and
introns.
http://highered.mcgrawhill.com/sites/9834092339/student_view0/chapter16/animation
_-_exon_shuffling.html
In human cells, about 40-60% of the genes are
known to exhibit alternative splicing.
http://www.dnalc.org/view/16940-AlternativeRNA-Splicing.html
http://www.youtube.com/watch?v=_9pROnSD-A
Translational Control; microRNAs