생명공학연구소 1차 세미나 안내
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◈ 주 제 : Dynamic changes of the DNA methylation and hydroxymethylation during neural differentiation of hES cells
◈ 연 사 : 김미랑 박사
◈ 소 속 : 한국생명공학연구원 유전체의학연구센터
◈ 일 시 : 2013년 4월 11일(목) 오전 11시
◈ 장 소 : 영남대학교 제3과학관 307호
< Abstract >
DNA methylation and hydroxymethylation have been implicated in normal development and differentiation, but our knowledge about the genome-wide distribution of 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC) during cellular differentiation remains limited. Using an in vitro model system of gradual differentiation of human embryonic stem (hES) cells into ventral midbrain-type neural precursor cells and terminally into dopamine neurons, we explored changes in 5mC or 5hmC patterns during lineage commitment. We found that a combination of three techniques, 450K DNA methylation array, MBD-seq, and hMeDIP-seq, provided comprehensive information on the genome-wide 5mC or 5hmC patterns. We observed dramatic genome-wide changes of 5mC patterns during differentiation of hES cells into neural precursor cells. Although global 5hmC distribution was more stable than 5mC during differentiation, the 5hmC pattern was dynamic in coding exons, CpG islands, and shores. In addition to the role of DNA methylation in initiating gene silencing, we also found that methylation acts as a locking mechanism to maintain gene silencing in our in vitro system. More than 1,000 genes, including those related to mesoderm development, acquired promoter methylation during neuronal differentiation even though they were already silenced in hES cells. Finally, we found that activated genes lost 5mC in their transcription start site but acquired 5hmC near their start site and gene body during differentiation. Our findings provide clues for elucidating the molecular mechanisms underlying lineage-specific differentiation of pluripotent stem cells during human embryonic development.
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