PMC:3589482 / 21921-24555 JSONTXT

{"target":"https://pubannotation.org/docs/sourcedb/PMC/sourceid/3589482","sourcedb":"PMC","sourceid":"3589482","source_url":"http://www.ncbi.nlm.nih.gov/pmc/3589482","text":"Sequence Conservation within the Human and Murine SerpinB2 Proximal Promoters\nTo look for potential cis-acting elements that might mediate transcription of the murine SerpinB2 gene and the response to LPS, we aligned the murine and human SerpinB2 5′ flanking regions. We reasoned that the presence of evolutionarily conserved, potential transcription factor binding sites in this region might play a role in the regulation of SerpinB2 gene expression [52]. The presence of several repetitive sequence elements delineated five broadly homologous regions (A-E) between the human and murine promoters (Fig. 2C). The proximal promoter (Region E), which contains the essential LPS response element, exhibited the greatest homology. Further analysis of Region E revealed that several of the cis-acting regulatory elements defined in the human SerpinB2 proximal promoter are conserved in the murine SerpinB2 promoter (Fig. 3). Specifically, a TATA consensus sequence is located 23 to 29bp upstream from the transcription initiation site, similar to the position of the TATA box of the human SERPINB2 gene [53]; [54]. A putative CCAAT enhancer binding protein (C/EBP) site is present at −192/−203, two potential activator protein 1 (AP-1) binding sites are found at nucleotides −88/−94 and −100/−106, and a putative cyclic AMP response element (CRE) is present at −172/−177. Both of the AP-1 sites are identical in sequence to those identified in the human SERPINB2 promoter, and the CRE differs in the identity of a single central nucleotide [37]; [55]. A consensus E box (−538/−533), as well as potential binding sites for PU.1 (−412/−407) and Oct-1 (−296/−288) were also identified within the proximal promoter region (Fig. S2). Further upstream, a retinoic acid response element at −1349/−1340, a PAUSE-1 silencer element at −1540/−1528 and a NF-κB p65 binding site at −1342/−1351 (Fig. S2) are also well conserved [16]; [30]; [56].\n10.1371/journal.pone.0057855.g003 Figure 3 Potential cis-acting regulatory elements in the LPS responsive region of the murine SerpinB2 promoter\n−563/−1. Mouse and human nucleotide sequences were aligned using Clustal W software. Cis-acting elements conserved between the human and murine SerpinB2 promoters are boxed and labeled. AP-1 =  activator protein 1; C/EBP =  CCAAT enhancer binding protein; CRE = cAMP response element; Oct1 =  octamer transcription factor 1/POU2F1; PU.1 =  purine box binding protein 1. The putative transcription initiation site (tis) is indicated and exon 1 is presented in uppercase. The location of the 5' ends of the −539, −189 and −87 reporter constructs are also 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