Transcriptional - These mechanisms prevent transcription. Posttranscriptional - These mechanisms...

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Transcript of Transcriptional - These mechanisms prevent transcription. Posttranscriptional - These mechanisms...

Page 1: Transcriptional - These mechanisms prevent transcription. Posttranscriptional - These mechanisms control or regulate mRNA after it has been produced.
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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.

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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=9AfBsTAQ8zsEpigenetics primer

http://www.youtube.com/watch?v=Xjq5eEslJhw&NR=1&feature=endscreen

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http://learn.genetics.utah.edu/content/epigenetics/nutrition/

Nutrition and epigenetics

SAM e: http://www.mayoclinic.com/health/same/NS_patient-same

Epigentic inheritance example X inactivation

http://www.youtube.com/watch?v=mHak9EZjySs

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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.

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Biological roles of acetylationHistone 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 manysolid tumors to the histone acetylation status. The loss of acetylation at Lys16 of H4 is a common characteristic ofhuman cancer. Hence, HATs and HDACs have become some of the most promising targets in cancer therapy.

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Role of DNA methylation is to silence the gene:

http://www.nature.com/scitable/topicpage/the-role-of-methylation-in-gene-expression-1070

Biological roles of DNA methylationIn the mammalian genome, about 70% of CpGdinucleotides 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 repressionand plays important roles in heterochromatin formation, long-term silencing of repetitive elements, X-chromosome inactivation and in the establishment and maintenance ofimprinted genes.

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Histone MethylationHistone methylation is a more stable modification thanacetylation

Biological roles of histone methylationRecent 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 intranscriptional regulation, cancer cell proliferation and normal neuronal function, and the loss of trimethylation at Lys20 of H4 in human cancer. Studies have suggestedthat histone demethylation and deacetylation are tightly coupled.

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http://www.youtube.com/watch?v=29doT6Hf2MI How methylation silences genes

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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=YjWuVrzvZYA

mRNA processing

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Post transcriptional modification:RNA modification: exons and introns.

http://highered.mcgraw-hill.com/sites/9834092339/student_view0/chapter16/animation_-_exon_shuffling.html

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In human cells, about 40-60% of the genes are known to exhibit alternative splicing.

http://www.dnalc.org/view/16940-Alternative-RNA-Splicing.html

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Translational Control; microRNAs

http://www.youtube.com/watch?v=_-9pROnSD-A