Role of Sp1 response element in transcription of the human transglutaminase 1 gene

Bart A. Jessen, Marjorie A. Phillips, Alain Hovnanian, Robert H. Rice

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

This study addresses the contribution of an Sp1 response element in the proximal promoter of the transglutaminase 1 gene to transcription in normal epidermis and in a case of lamellar ichthyosis lacking transglutaminase 1 activity. The latter exhibited an Sp1 promoter mutation previously hypothesized to suppress transcription. In this study, several experiments indicated that the native Sp1 response element was functional, but it had only a small influence on transcription, and the previously observed mutation had no effect. These experiments involved mobility shift assays and transfections of promoter constructs in which the Sp1 site was mutated or lacking altogether. In addition the proximal 1.6 kb of the promoter from the affected individual was as active in transfections as the promoter from unaffected individuals. A search for sequence alterations in mRNA transcribed in keratinocytes from the patient revealed a novel single base mutation in codon 661 of the transglutaminase coding region predicted to result in premature termination of protein translation. The presence of this mutation in parental genomic DNA was confirmed by restriction digestion. Thus the lamellar ichthyosis phenotype in this case is likely attributable to a novel non-sense mutation in the coding region leading to reduced transglutaminase 1 mRNA levels rather than mutation of the Sp1 site.

Original languageEnglish (US)
Pages (from-to)113-117
Number of pages5
JournalJournal of Investigative Dermatology
Volume115
Issue number1
DOIs
StatePublished - 2000

Fingerprint

Response Elements
Transcription
Genes
Mutation
Lamellar Ichthyosis
Messenger RNA
Transglutaminases
Translational Peptide Chain Termination
Transfection
Assays
Experiments
DNA
Electrophoretic Mobility Shift Assay
Keratinocytes
Epidermis
Codon
transglutaminase 1
Digestion
Proteins
Phenotype

Keywords

  • Keratinocyte transglutaminase
  • Lamellar ichthyosis
  • Non-sense mutation
  • Transglutaminase

ASJC Scopus subject areas

  • Dermatology

Cite this

Role of Sp1 response element in transcription of the human transglutaminase 1 gene. / Jessen, Bart A.; Phillips, Marjorie A.; Hovnanian, Alain; Rice, Robert H.

In: Journal of Investigative Dermatology, Vol. 115, No. 1, 2000, p. 113-117.

Research output: Contribution to journalArticle

Jessen, Bart A. ; Phillips, Marjorie A. ; Hovnanian, Alain ; Rice, Robert H. / Role of Sp1 response element in transcription of the human transglutaminase 1 gene. In: Journal of Investigative Dermatology. 2000 ; Vol. 115, No. 1. pp. 113-117.
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