Functional Profiling of Human MeCP2 by Automated Data Comparison Analysis and Computerized Expression Pathway Modeling

김인주; 이신해; 정진우; 박준형; 유미애; 김철민

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자료유형: 학술저널

저자정보: 김인주 이신해 정진우 박준형 유미애 김철민

저널정보: 대한의료정보학회 Healthcare Informatics Research Healthcare Informatics Research 제22권 제2호

발행연도: 2016.1

수록면: 120 - 128 (9page)

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Objectives: 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.

#Rett Syndrome #Methyl-CpG-Binding Protein 2 #Carcinogenesis #Microarray Analysis #Transcription Factors

참고문헌 (38)

참고문헌 신청

Rett A / 1966 / Uber ein eigenartiges hirnatrophisches Syndrom bei Hyperammonamie im Kindesalter / Wien Med Wochenschr 116(37):723~726

Hoffbuhr K / 2001 / MeCP2 mutations in children with and without the phenotype of Rett syndrome / Neurology 56(11):1486~1495

Imessaoudene B / 2001 / MECP2 mutation in nonfatal, non-progressive encephalopathy in a male / J Med Genet 38(3):171~174

Jaenisch R / 2003 / Epigenetic regulation of gene expression:how the genome integrates intrinsic and environmental signals / Nat Genet 33:245~254

Bernard D / 2006 / The methyl-CpG-binding protein MECP2is required for prostate cancer cell growth / Oncogene 25(9):1358~1366

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