Transcriptional regulation of epidermal-specific cell adhesion molecules

Stephanie A Silos, Thomas Jefferson University

Abstract

The appropriate temporal and spatial specific expression of cell adhesion molecules is required for many physiologic functions including embryogenesis, tissue formation, and tissue maintenance. Abrogation of the exquisitely regulated spatial and temporal expression of cell adhesion molecules has been correlated with human pathology including: abnormal pregnancies, abnormal fetal development, and cancer. In an effort to elucidate the complexities of transcriptional regulation of cell-adhesion molecules, the expression of two epidermal-restricted molecules, bullous pemphigoid antigen 1 (BPAG1) and pemphigus vulgaris antigen (PVA), were studied. These molecules were chosen because they are expressed in the epidermis--a tissue which provides an excellent system to study human transcriptional regulation. BPAG1 is the major antigen in the autoimmune blistering skin disease bullous pemphigoid. It encodes a 230 kDa protein which is important in the hemidesmosomal plaque, anchoring keratinocytes to the underlying basement membrane. PVA is a 130 kDa transmembrane glycoprotein with homology to the cadherin gene superfamily which participates in desmosomal cell adhesion primarily at the level of the stratum spinosum. In order to study the expression of these molecules the DNA encoding their transcriptional regulation was isolated. The BPAG1 functional promoter and 2800 bp of 5$\sp\prime$ flanking DNA had previously been isolated, and a cis-element, KRE2, important in BPAG1 epidermal specific expression had been characterized (Tamai, et al. 1993, Tamai, et al. 1994). Through the work of this thesis, the PVA genomic gene was identified, its intron-exon organization was characterized and 2800 bp of 5$\sp\prime$ flanking DNA was sequenced. The functional PVA promoter was identified within the 5$\sp\prime$ flanking DNA. Both the BPAG1 and PVA 5$\sp\prime$ flanking region were analyzed and novel cis-elements participating in epidermal transcriptional regulation were identified. Preliminary characterization of the transcription factor which binds to BPAG1 cis-element, KRE3, was initiated. Comparison of the transcriptional regulation of BPAG1 and PVA with other members of their gene superfamily or with other epidermally expressed genes revealed a number of similarities with a few distinct differences. The global mechanism of epidermal specific regulation appeared similar while the individual cis-elements and transcription factors were different.

Subject Area

Molecular biology

Recommended Citation

Silos, Stephanie A, "Transcriptional regulation of epidermal-specific cell adhesion molecules" (1996). ETD Collection for Thomas Jefferson University. AAI9633541.
https://jdc.jefferson.edu/dissertations/AAI9633541

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