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Guidelines and Assignments (Dec 8, 104) “Epigenetic regulation in cancer--a focus on DNA methylation and gene silencing” (you are prohibited to use X chromosome as an example ! ) Prepare powerpoint slides in a CD (each presentation should be labeled by the names of the contributors, 10-12 slides suggested for each presentation) for no more than 10 min presentation time, turn in one copy of the CD to 呂政展老師 in Dept of Pathology(病理科) and one copy of the CD to 蔣輯武老師, no later than 1 PM on Monday (Dec. 7 逾時扣分). Note: 1. It is preferable to answer those questions with examples and figures. 2. It is highly recommended that these examples have background information (ie, introduction), purposes of the study, methods used to answer the specific aims, results, the interpretation and the conclusion obtained. 3. The sources (ie, cited references) of examples should be given at the bottom of the each powerpoint slide. 4. The references should be included in the CD. Note that it is strongly recommended not to use Wikipedia. If you have any questions, please address to 呂政展老師 at [email protected] or ext. 2641 or to 蔣輯武老師 at [email protected] ext 3637 1. (MT1) A. How is the 5-mC distributed within the human genome? B. Do all human genes have CpG island at their promoters? C. How bisulfite treatment may affect the CpG methylation status? D. What methods can be used to detect the methylation status of DNA? Please describe at least four different methods which must include one using next generation sequencing (NGS). And explain its principle and its mechanistic action. 2. (IMM1) There is an inverse correlation between DNA methylation and gene expression and transcription. This has been unambiguously demonstrated in cancer cells. Does this DNA methylation also occur in normal tissues (Note : Don’t use X chromosome as an example !)? If so, please give an example and show the relevant molecular mechanisms and evidence. 3. (MT2 ) and (IMM2) How DNA methylation (not chromatin methylation) may affect the gene expression? Different molecular mechanisms have been identified, please give a little bit detailed explanation of their molecular mechanisms; give examples to illustrate your points. 4. (MT3 ) Different DNA methyltransferases (DNMTs) are known to mediate the various DNA methylation processes. Please describe their specific functions and roles in the DNA methylation and their mechanisms. 5. (IMM3) There is molecular link and evidence that histone modifications may be linked to DNA methylation. Please give an example to illustrate this event. 6. (MT4) What is CpG island methylator phenotype (CIMP)? What are the characteristics of the CIMP? What diseases are associated with CIMP? 7. (IMM4) In a given cancer, can both gene mutations and gene silencing by DNA methylation occur simultaneously in a given cancer tissue? Please use examples to describe how the patterns of both these processes may resemble or differ from each other in targets, signal pathways, cancer subtypes, etc.