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Dissertation zugänglich unter
URN: urn:nbn:de:gbv:18-31600
URL: http://ediss.sub.uni-hamburg.de/volltexte/2007/3160/


Identification and Characterization of the Promoter Region of the SLA/LP Gene

Identifikation und Charakterisierung der Promoterregion des SLA/LP Gens

Wang, Chunxia

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 Dokument 1.pdf (957 KB) 


SWD-Schlagwörter: Promotor <Genetik> , Genregulation , Transkription <Genetik> , Hepatitis , Autoimmunität
Basisklassifikation: 44.61 , 44.45
Institut: Medizin
DDC-Sachgruppe: Medizin, Gesundheit
Dokumentart: Dissertation
Hauptberichter: Lohse, Ansgar W. (Prof. Dr.)
Sprache: Englisch
Tag der mündlichen Prüfung: 19.12.2006
Erstellungsjahr: 2006
Publikationsdatum: 02.01.2007
Kurzfassung auf Englisch: Anti-SLA/LP antibodies are thus far the only known autoantibody, which are specific markers of autoimmune hepatitis (AIH) with 100% specificity and 20% sensitivity (Wies et al. 2000). However, the function, regulation of expression and the pathogenetic role of SLA/LP are not clear. It will be helpful for understanding autoimmunity to SLA/LP and the pathogenesis of AIH, if we knew more about SLA/LP. The SLA/LP protein is expressed widely in different normal tissues and mouse SLA/LP mRNA can be detected as early as day 7 of embryonic development. Therefore, it seems to have a role during embryogenesis and in the function of adult tissues. In this study, we focused on the transcriptional regulation of murine SLA/LP protein. We mapped the core promoter region of the SLA/LP gene, which is located at -99 to -37 flanking the 5’-end of transcription start site. Within this core promoter, a Sp1 binding site, a Sp1-like binding site and a possible RAP1 binding site was identified. All of these cis-activating elements are essential for maintaining the basic initiation of transcription of SLA/LP protein. 75bp upstream of this core promoter, there is an Oct-1 binding site that acts as a repressor down-regulating the expression of SLA/LP protein. SLA/LP gene promoter is a CpG island promoter, which normally contains multiple transcription start sites. This promoter lacks typical core promoter elements, such as TATA box, Inr, DPE and BRE. The structure of the SLA/LP promoter is a multiple regulator architecture that means that the SLA/LP gene is regulated in a complicated combinational way. The expression of SLA/LP protein seems to be the result of balance between activator Sp1/RAP1 and repressor Oct-1. SLA/LP has also been confirmed to be an important protein during embryonic development. The non-tissue specific expression of SLA/LP protein may be due to the nontissue specific transcription factors. The concentration and activity of these factors as well as some liver/pancreas specific signals may contribute to the translation frequency of SLA/LP protein in different tissues. The expression pattern and the promoter features suggest strongly that the mouse SLA/LP gene may be a housekeeping gene.

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