Multiple regulatory regions and tissue-specific transcription initiation mediate the expression of NEMO/IKKgamma gene.
NEMO/IKKgamma gene, which is responsible of two allelic diseases in human, EDA-ID and IP, encodes for a protein with a central regulatory role in the activation of the NF-kB pathway. We here provide insights into the molecular mechanism governing NEMO/IKKgamma expression. We mapped 4 distinctive NEMO/IKKgamma transcription start sites each corresponding to an alternative first exon, controlled by two conserved promoters. A distal promoter, named promoter A, located 10 kb upstream of the coding region and a proximal promoter, promoter B, with strong bi-directional activity driving also the transcription of G6PD gene in the opposite direction. The promoter B is housekeeping, it is embedded in a CpG island, required for proper expression and it is down-regulated by methylation. The promoter A is active in cells of hepatic origin and it directs transcription of the main NEMO/IKKgamma 5' UTR alternative transcript in liver, which starts at a tissue-specific site. Qualitative and quantitative expression analysis revealed that each NEMO/IKKgamma 5' UTR alternative transcript has different expression profiles indicating that the control of NEMO/IKKgamma expression is mediated through tissue-specific transcription initiation sites and multiple regulatory regions.
Fusco
Francesca
F
Institute of Genetics and Biophysics Adriano Buzzati-Traverso (IGB-CNR), Via P. Castellino 111, 80131, Naples, Italy.
Mercadante
Vincenzo
V
Miano
Maria Giuseppina
MG
Ursini
Matilde Valeria
MV
D020121:5' Untranslated Regions; D017398:Alternative Splicing; D001483:Base Sequence; D002460:Cell Line; D019295:Computational Biology; D004247:DNA / Q000235:genetics; D044127:Epigenesis, Genetic; D005091:Exons; D015870:Gene Expression; D005809:Genes, Regulator; D006367:HeLa Cells; D006801:Humans; D051550:I-kappa B Kinase / Q000235:genetics*; D008099:Liver / Q000378:metabolism; D008214:Lymphocytes / Q000378:metabolism; D011401:Promoter Regions, Genetic; D014018:Tissue Distribution; D014158:Transcription, Genetic
D020121:5' Untranslated Regions; C491731:IKBKG protein, human; D004247:DNA; D051550:I-kappa B Kinase