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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. 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 zs 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