Journal of Life Science (생명과학회지)

Korean Society of Life Science (한국생명과학회)
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In Silico Analysis of Gene Function and Transcriptional Regulators Associated with Endoplasmic Recticulum (ER) Stress

Endoplasmic recticulum stress와 관련된 유전자기능과 전사조절인자의 In silico 분석

  • Kim, Tae-Min (School of Oriental Medicine, Pusan National University) ;
  • Yeo, Ji-Young (School of Oriental Medicine, Pusan National University) ;
  • Park, Chan-Sun (Korea Research Institute of Bioscience and Biotechnology) ;
  • Rhee, Moon-Soo (Korea Research Institute of Bioscience and Biotechnology) ;
  • Jung, Myeong-Ho (School of Oriental Medicine, Pusan National University)
  • 김태민 (부산대학교 한의학전문대학원) ;
  • 여지영 (부산대학교 한의학전문대학원) ;
  • 박찬선 (한국생명공학연구원) ;
  • 이문수 (한국생명공학연구원) ;
  • 정명호 (부산대학교 한의학전문대학원)
  • Published : 2009.08.30
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Abstract

It has been postulated that endoplasmic (ER) stress is involved in the development of several diseases. However, the detailed molecular mechanisms have not been fully understood. Therefore, we characterized a genetic network of genes induced by ER stress using cDNA microarray and gene set expression coherence analysis (GSECA), and identified gene function as well as several transcription regulators associated with ER stress. We analyzed time-dependent gene expression profiles in thapsigargin-treated Sk-Hep1 using an oligonucleotide expression chip, and then selected functional gene sets with significantly high expression coherence which was processed into functional clusters according to the expression similarities. The functions related to sugar binding, lysosome, ribosomal protein, ER lumen, and ER to golgi transport increased, whereas the functions with mRNA processing, DNA replication, DNA repair, cell cycle, electron transport chain and helicase activity decreased. Furthermore, functional clusters were investigated for the enrichment of regulatory motifs using GSECA, and several transcriptional regulators associated with regulation of ER-induced gene expression were found.

ER stress에 관련된 유전자의 기능변화와 전사조절인자 분석하기 위해 ER stress를 유도한 간세포에서 expression microarray로 유전자 발현을 확보한 후 GSECA로 분석하였다. ER stress가 유도되면, ER에 주어지는 과도한 부하를 감소시키는 기능들이 증가하는 반면, ER stress가 더 증가함에 따라 ATP 생성이나 DNA repair, 더 나아가 세포분열의 기능이 감소하는 등 세포가 damage을 받음을 알 수 있었다. ER stress에 관련된 전사조절인자로는 FOX04, AP-1, FOX03, HNF4, IRF-1, GATA 등의 전사조절인자들이 ER stress에 의해 발현이 증가하는 유전자들의 promoter에 공통적으로 존재하였으며, E2F, Nrf-1, Elk-1, YY1, CREB, MTF-1, STAT-1, ATF 등의 전사인자들이 발현이 감소하는 유전자들의 promoter에서 공통적으로 존재하여, 이들의 전사인자들이 ER stress에 의한 유전자의 발현조절에 중요한 역할을 하는 전사조절인자임을 알 수 있었다.

Keywords

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