Genomic organization and promoter characterization of the gene encoding a putative endoplasmic reticulum chaperone, ERp29

Ernest Sargsyan, Mikhail Baryshev, Maria Backlund, Anatoly Sharipo, Souren Mkrtchian

Research output: Contribution to journalArticlepeer-review

33 Citations (Scopus)

Abstract

ERp29 is a soluble protein localized in the endoplasmic reticulum (ER) of eukaryotic cells, which is conserved in all mammalian species. The N-terminal domain of ERp29 displays sequence and structural similarity to the protein disulfide isomerase despite the lack of the characteristic double cysteine motif. Although the exact function of ERp29 is not yet known, it was hypothesized that it may facilitate folding and/or export of secretory proteins in/from the ER. ERp29 is induced by ER stress, i.e. accumulation of unfolded proteins in the ER. To gain an insight into the mechanisms regulating ERp29 expression we have cloned and characterized the rat ERp29 gene and studied in details its distribution in human tissues. Comparison with the murine and human genes and phylogenetic analysis demonstrated common origin and close ortholog relationships of these genes. Additionally, we have cloned ∼3 kb of the 5′-flanking region of the ERp29 gene and functionally characterized its promoter. Such characteristics of the promoter as GC-rich sequence, absence of TATA-box, multiple transcription start sites taken together with the ubiquitous gene expression, reaching maximum levels in the specialized secretory tissues, indicate that ERp29 belongs to the group of the constitutively expressed housekeeping genes. A 337 bp fragment of the 5′ flank was identified as a core promoter sufficient for the transcriptional activation of the gene. Gel mobility shift assay indicated interaction of the predicted GC and E box elements within the core promoter with Sp1/Sp3 and USF1/USF2 transcription factors, respectively, suggesting their key role in the basal expression of the gene.

Original languageEnglish
Pages (from-to)127-139
Number of pages13
JournalGene
Volume285
Issue number1-2
DOIs
Publication statusPublished - 20 Feb 2002
Externally publishedYes

Keywords*

  • Chaperone
  • Housekeeping gene
  • Promoter
  • Transcriptional regulation

Field of Science*

  • 1.6 Biological sciences

Publication Type*

  • 1.1. Scientific article indexed in Web of Science and/or Scopus database

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