Genome-wide screening of dioxin-responsive genes in fetal brain: Bioinformatic and experimental approaches

Hideki Fujita, Hazuki Samejima, Noriyuki Kitagawa, Takayuki Mitsuhashi, Takanori Washio, Junzo Yonemoto, Masaru Tomita, Takao Takahashi, Kenjiro Kosaki

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Many of the effects of dioxins, which are potent environmental pollutants and teratogens, are mediated through the aryl hydrocarbon receptor, also known as the dioxin receptor. The purpose of the present study was to characterize dioxin-responsive genes in a comprehensive manner using two complementary approaches: bioinformatic analysis and microarray analysis. First, we characterized the overall distribution of the cis-regulatory element for the dioxin-responsive element sequence (DRE) 'gcgtg' within putative promoter regions. We assembled the upstream sequences 10 kb from the transcription start site and evaluated their location and frequency in the human and mouse genomes. Second, we characterized the expression profile of mouse embryonic day 12 fetal brain exposed to 2,3,7,8-tetrarchlorodibenzo-p-dioxin. The distributions of 26 680 DREs among 2843 human genes and 98 711 DREs among 18 541 mouse genes were examined. In both species, the DREs tended to be located close to the transcription start site. Forty genes exhibited significant induction or repression following dioxin exposure in fetal mice. The set of genes exhibited a strong functional coherence, with statistically significant enrichment in organogenesis and the DNA-dependent regulation of transcription, according to Gene Ontology annotations. In both humans and mice, DREs were preferentially distributed close to transcription start sites. Evolutionary conservation of this unique DRE distribution pattern suggests that DREs may be involved in transcriptional regulation. In mice, prenatal dioxin exposure altered the expression of 10 transcription factors, many of which have been documented to play a role in organogenesis. These genes may represent potential mediators of dioxin's effects in fetal tissues.

Original languageEnglish
Pages (from-to)135-143
Number of pages9
JournalCongenital Anomalies
Volume46
Issue number3
DOIs
Publication statusPublished - 2006 Sep

Fingerprint

Dioxins
Computational Biology
Genome
Transcription Initiation Site
Brain
Genes
Aryl Hydrocarbon Receptors
Organogenesis
Teratogens
Molecular Sequence Annotation
Environmental Pollutants
Gene Ontology
Human Genome
Microarray Analysis
Genetic Promoter Regions
Fetus
Transcription Factors
DNA

Keywords

  • Dioxin
  • Microarray
  • Promoter
  • TCDD
  • Teratogen

ASJC Scopus subject areas

  • Developmental Biology

Cite this

Genome-wide screening of dioxin-responsive genes in fetal brain : Bioinformatic and experimental approaches. / Fujita, Hideki; Samejima, Hazuki; Kitagawa, Noriyuki; Mitsuhashi, Takayuki; Washio, Takanori; Yonemoto, Junzo; Tomita, Masaru; Takahashi, Takao; Kosaki, Kenjiro.

In: Congenital Anomalies, Vol. 46, No. 3, 09.2006, p. 135-143.

Research output: Contribution to journalArticle

Fujita, Hideki ; Samejima, Hazuki ; Kitagawa, Noriyuki ; Mitsuhashi, Takayuki ; Washio, Takanori ; Yonemoto, Junzo ; Tomita, Masaru ; Takahashi, Takao ; Kosaki, Kenjiro. / Genome-wide screening of dioxin-responsive genes in fetal brain : Bioinformatic and experimental approaches. In: Congenital Anomalies. 2006 ; Vol. 46, No. 3. pp. 135-143.
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