Ramakrishna Suresh
Dong Ho KIM
2019-02-28T03:04:44Z
2019-02-28T03:04:44Z
2019-02
https://repository.hanyang.ac.kr/handle/20.500.11754/99945
http://hanyang.dcollection.net/common/orgView/200000434791
Ubiquitination in intracellular functions has been studied in the context of poly-ubiquitination that is essential for marking proteins for degradation through the ubiquitin-proteasome pathway (UPP). Recent discoveries have shown key cellular roles for mono-ubiquitination, including epigenetic changes of chromatin. Mono-ubiquitination of histone 2A (H2A) and histone 2B (H2B) is one of the major histone modification in mammalian cells. Ubiquitin is a much larger molecules than other posttranslational modifications, such as acetyl- and methyl- group, and thus has important steric consequences for the nucleosome.
Embryonic Stem Cells (ESCs) has pluripotency, which is essential for initiating various differentiation pathways. Epigenetic modification of chromatin is a key cellular factor affecting ESC’s characteristics such as maintaining or differentiation of stem cell pluripotency. Several studies reported that dissociation of ubiquitin molecules from H2A or H2B catalyzed by several Deubiquitinating Enzymes (DUBs) have diverse effect on gene expression. Moreover, these DUBs are expected to have a role in embryonic stem cell’s pluripotency maintenance or differentiation ability. In this research, we reported that the effects of altered mono-ubiquitination patterns of H2B on Lys120 resulted by CRISPR/Cas9 mediated knockout of several deubiquitinating enzymes during P19 cell’s neuronal differentiation. Furthermore, we reported that the differential expression of several genes which have critical role in neuronal differentiation.
When ubiquitin specific protease 7 (USP7) was knocked out in p19 cells, increased expression of lineage specific markers including Sox10, GFAP and Olig2 which are responsible for gliogenesis were observed. Taken together, in this study we demonstrated that USP7 alters histone 2B mono-ubiquitination and regulates neuronal differentiation by elevating the expression of glial progenitor lineage transcription factors.
한양대학교
USP7 alters histone 2B mono-ubiquitination and regulates mouse neurogenesis by elevating the expression of glial progenitor lineage transcription factors
신경분화 중 탈유비퀴틴화 효소 USP7의 넉아웃에 의한 히스톤단백질 2B의 모노유비퀴틴 패턴 및 신경교세포 전사인자의 발현 변화 연구
Theses
김동호
김동호
S
의생명공학전문대학원
의생명과학과
Doctor