Transcriptional control of occludin expression in vascular endothelia: Regulation by Sp3 and YY1

Abstract

Endothelium differentiates in response to tissue-specific signals; brain endothelium expresses tight junctions and transporters which are absent from other endothelia. The promoter of the tight junction protein occludin exhibited strong activity in a brain endothelial cell line, hCMEC/D3 but was inactive in lung endothelial cells. Expression of occludin in brain endothelium corresponded with binding of Sp3 to a minimal promoter segment close to the transcription-start site. However, in lung endothelium Sp-transcription factors did not bind to this site although they are present in the cell nucleus. In contrast, repression of occludin in lung endothelium was associated with the binding of YY1 to a remote site in the promoter region, which was functionally inactive in brain endothelium. The work identified a group of transcription factors including Sp3 and YY1, which differentially interact with the occludin promoter to induce expression of occludin in brain endothelium and repression in other endothelia. The mechanism controlling occludin expression is similar to that which controls tissue-specific expression of the transferrin receptor in brain endothelium, leading to a scheme for endothelial differentiation, in which activation or repression of tissue-specific proteins is maintained by a set of transcription factors which include Sp3 and YY1.

Membrane-Initiated Estradiol Signaling of Epithelial-Mesenchymal Transition-Associated Mechanisms Through Regulation of Tight Junctions in Human Breast Cancer Cells

“…Estrogen significantly inhibits occludin expression at the mRNA and protein level after 24 h. This was consistent with previous reports showing that estrogens are able to regulate occludin expression through ER beta in intestinal epithelial cells [42,43]. Sade et al were the first to describe the occludin promoter and suggested tissue type-dependent expression.…”

“…Sade et al were the first to describe the occludin promoter and suggested tissue type-dependent expression. Occludin gene expression is augmented in brain endothelium and decreased in other endothelia in the presence of the same transcription factors, suggesting that ER beta might be a putative co-repressor in the occludin promoter [42].…”

Claudin-6, 7, or 9 Overexpression in the Human Gastric Adenocarcinoma Cell Line AGS Increases Its Invasiveness, Migration, and Proliferation Rate

“…The ZO-1 expression was apparently higher in claudin-2-and claudin-6-overexpressing cells, whereas confocal microscopy results showed an enhanced membrane-associated expression of ZO-1 in the AGS cells overexpressing claudin-9 and claudin-7. It is well known that the transcription factors regulating the occludin and ZO-1 expression are different from those that regulate claudin expression (44,45). Nevertheless, it has been recently shown that the activation of the oncogenic Raf-1 protein, which regulates occludin expression, confers an oncogenic phenotype in Pa-4 epithelial cells (46).…”

Claudin and occludin expression and function in the seminiferous epithelium

“…In vascular endothelial cells, promoter analyses revealed that glucocorticoid receptor is important for occludin expression (Felinski et al 2008;Harke et al 2008). Activation by the transcription factor Sp3 and repression by YY1 are important for differential expression of occludin in various endothelial beds (Sade et al 2009). …”