2021학년도 1학기 제 4회 CNS 융합세미나 안내입니다.
• 날짜 : 2021년 4월 29일 목요일 오후 12시
• 연사 : 의생명시스템학부 임도환 교수
• 장소 : 온라인 ZOOM 세미나 ( Link :
• 제목 : Gene regulation and Sequencing technologies
• 초록 :
[Part I]
The steroid hormone ecdysone is the central regulator of insect metamorphosis, during which a growing, immature larva is remodeled, through pupal stages, to a reproductive adult. However, the underlying mechanisms of ecdysone-mediated metamorphosis remain to be fully elucidated. Here, we identified metamorphosis-associated microRNAs (miRNAs) and their potential targets by cross-linking immunoprecipitation coupled with deep sequencing of endogenous Argonaute 1 protein in Drosophila. Interestingly, miR-8-3p targeted five Vha genes encoding distinct subunits of vacuolar H+-ATPase (V-ATPase), which has a vital role in the organellar acidification. The expression of ecdysone-responsive miR-8-3p is normally downregulated during Drosophila metamorphosis, but temporary overexpression of miR-8-3p in the whole body at the end of larval development led to defects in metamorphosis and survival, hallmarks of aberrant ecdysone signaling. In addition, miR-8-3p was expressed in the prothoracic gland (PG), which produces and releases ecdysone in response to prothoracicotropic hormone (PTTH). Notably, overexpression of miR-8-3p or knockdown of its Vha targets in the PG resulted in larger than normal, ecdysone-deficient larvae that failed to develop into the pupal stage but could be rescued by ecdysone feeding. Moreover, these animals showed defective PTTH signaling with a concomitant decrease in the expression of ecdysone biosynthetic genes. We also demonstrated that the regulatory network between the conserved miR-8-3p/miR-200 family and V-ATPase was functional in human cells. Consequently, our data indicate that the coordinated regulation of V-ATPase subunits by miR-8-3p is involved in Drosophila metamorphosis by controlling the ecdysone biosynthesis.
[Part II]
In eukaryotes, gene expression is elaborately regulated in 3D genome structure composed of the connectivity of thousands of the regulatory elements. Hormone exerts powerful effects on various physiological processes through controlling gene expression. However, the comprehensive understanding of hormone effects on gene regulation and 3D promoter-enhancer networks remains poorly understood. Here, we simultaneously generated the gene expression profile and promoter-enhancer interaction map using GRID-seq under estrogen hormone (E2) treated condition. Genes responded to E2 with differential strength and expression patterns, associating with dynamic alteration of transcription hub. Interestingly, regardless of the direction of alteration, E2-responsive genes were predominantly connected with ERa-bound regulatory elements but exhibiting different features for determining the alteration direction. Furthermore, we found that the E2/ERa-direct target genes showed quick and robust responses to E2 and were also involved in distinct biological functions. Remarkably, many interconnected E2-resonsive genes were cooperatively orchestrated and appeared a “community effect” in the same transcription hub in terms of the expression. Together, our data provide insights into gene expression regulated in the transcription hub by hormone.
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