title: Functional Profiling of Human MeCP2 by Automated Data Comparison Analysis and Computerized Expression Pathway Modeling.
abstract: OBJECTIVE
  Methyl-CpG binding protein 2 (MeCP2) is a ubiquitous epigenetic factor that represses gene expression by modifying chromatin. Mutations in the MeCP2 gene cause Rett syndrome, a progressive neurodevelopmental disorder. Recent studies also have shown that MeCP2 plays a role in carcinogenesis. Specifically, functional ablation of MeCP2 suppresses cell growth and leads to the proliferation of cancer cells. However, MeCP2's function in adult tissues remains poorly understood. We utilized a weight matrix-based comparison software to identify transcription factor binding site (TFBS) of MeCP2-regulated genes, which were recognized by cDNA microarray analysis.
  
  
  METHODS
  MeCP2 expression was silenced using annealed siRNA in HEK293 cells, and then a cDNA microarray analysis was performed. Functional analysis was carried out, and transcriptional levels in target genes regulated by MeCP2 were investigated. TFBS analysis was done within genes selected by the cDNA microarray analysis, using a weight matrix-based program and the TRANSFAC 6.0 database.
  
  
  RESULTS
  Among the differentially expressed genes with a change in expression greater than two-fold, 189 genes were up-regulated and 91 genes were down-regulated. Genes related to apoptosis and cell proliferation (JUN, FOSL2, CYR61, SKIL, ATF3, BMABI, BMPR2, RERE, and FALZ) were highly up-regulated. Genes with anti-apoptotic and anti-proliferative functions (HNRPA0, HIS1, and FOXC1) were down-regulated. Using TFBS analysis within putative promoters of novel candidate target genes of MeCP2, disease-related transcription factors were identified.
  
  
  CONCLUSIONS
  The present results provide insights into the new target genes regulated by MeCP2 under epigenetic control. This information will be valuable for further studies aimed at clarifying the pathogenesis of Rett syndrome and neoplastic diseases.
authors.affiliation: Department of Emergency Medical Technology, Dong-Eui Institute of Technology, Busan, Korea.
authors.forename: Injoo
authors.initials: I
authors.lastname: Kim
authors.affiliation: Department of Biological Sciences, Inha University, Incheon, Korea.
authors.forename: Shin Hae
authors.initials: SH
authors.lastname: Lee
authors.affiliation: Department of Emergency Medicine, Dong-A University College of Medicine, Busan, Korea.
authors.forename: Jinwoo
authors.initials: J
authors.lastname: Jeong
authors.affiliation: Codes Division, Insilicogen Inc., Suwon, Korea.
authors.forename: Jun Hyung
authors.initials: JH
authors.lastname: Park
authors.affiliation: Department of Molecular Biology, Pusan National University, Busan, Korea.
authors.forename: Mi Ae
authors.initials: MA
authors.lastname: Yoo
authors.affiliation: Supercomputing Center, Pusan National University, Busan, Korea.; Research Center for Anti-Aging Technology Development, Pusan National University, Busan, Korea.; Department of Medical Informatics, Pusan National University School of Medicine, Yangsan, Korea.
authors.forename: Cheol Min
authors.initials: CM
authors.lastname: Kim
keywords: Carcinogenesis; Methyl-CpG-Binding Protein 2; Microarray Analysis; Rett Syndrome; Transcription Factors