title: CHRFAM7A: a human-specific α7-nicotinic acetylcholine receptor gene shows differential responsiveness of human intestinal epithelial cells to LPS.
abstract: The human genome contains a unique, distinct, and human-specific α7-nicotinic acetylcholine receptor (α7nAChR) gene [CHRNA7 (gene-encoding α7-nicotinic acetylcholine receptor)] called CHRFAM7A (gene-encoding dup-α7-nicotinic acetylcholine receptor) on a locus of chromosome 15 associated with mental illness, including schizophrenia. Located 5' upstream from the "wild-type" CHRNA7 gene that is found in other vertebrates, we demonstrate CHRFAM7A expression in a broad range of epithelial cells and sequenced the CHRFAM7A transcript found in normal human fetal small intestine epithelial (FHs) cells to prove its identity. We then compared its expression to CHRNA7 in 11 gut epithelial cell lines, showed that there is a differential response to LPS when compared to CHRNA7, and characterized the CHRFAM7A promoter. We report that both CHRFAM7A and CHRNA7 gene expression are widely distributed in human epithelial cell lines but that the levels of CHRFAM7A gene expression vary up to 5000-fold between different gut epithelial cells. A 3-hour treatment of epithelial cells with 100 ng/ml LPS increased CHRFAM7A gene expression by almost 1000-fold but had little effect on CHRNA7 gene expression. Mapping the regulatory elements responsible for CHRFAM7A gene expression identifies a 1 kb sequence in the UTR of the CHRFAM7A gene that is modulated by LPS. Taken together, these data establish the presence, identity, and differential regulation of the human-specific CHRFAM7A gene in human gut epithelial cells. In light of the fact that CHRFAM7A expression is reported to modulate ligand binding to, and alter the activity of, the wild-type α7nAChR ligand-gated pentameric ion channel, the findings point to the existence of a species-specific α7nAChR response that might regulate gut epithelial function in a human-specific fashion.
authors: *Division of Trauma, Surgical Critical Care, Burns, and Acute Care Surgery, Department of Surgery, University of California, San Diego Health Sciences, San Diego, California, USA; and Cardiovascular Research Center, Luzhou Medical College, Luzhou, Sichuan, China.
authors: Xitong
authors: X
authors: Dang
authors: *Division of Trauma, Surgical Critical Care, Burns, and Acute Care Surgery, Department of Surgery, University of California, San Diego Health Sciences, San Diego, California, USA; and Cardiovascular Research Center, Luzhou Medical College, Luzhou, Sichuan, China.
authors: Brian P
authors: BP
authors: Eliceiri
authors: *Division of Trauma, Surgical Critical Care, Burns, and Acute Care Surgery, Department of Surgery, University of California, San Diego Health Sciences, San Diego, California, USA; and Cardiovascular Research Center, Luzhou Medical College, Luzhou, Sichuan, China anbaird@ucsd.edu.
authors: Andrew
authors: A
authors: Baird
authors: *Division of Trauma, Surgical Critical Care, Burns, and Acute Care Surgery, Department of Surgery, University of California, San Diego Health Sciences, San Diego, California, USA; and Cardiovascular Research Center, Luzhou Medical College, Luzhou, Sichuan, China.
authors: Todd W
authors: TW
authors: Costantini
mesh_terms: D020121:5' Untranslated Regions / Q000235:genetics; D018938:Caco-2 Cells; D002460:Cell Line; D045744:Cell Line, Tumor; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects*; D045325:HCT116 Cells; D019073:HT29 Cells; D006801:Humans; D015151:Immunoblotting; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000166:cytology / Q000187:drug effects*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D011401:Promoter Regions, Genetic / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D064569:alpha7 Nicotinic Acetylcholine Receptor / Q000235:genetics* / Q000378:metabolism
chemical_list: D020121:5' Untranslated Regions; C579167:Chrna7 protein, human; D008070:Lipopolysaccharides; D064569:alpha7 Nicotinic Acetylcholine Receptor
keywords: CHRNA7; dup-α7nAChR; human-specific genes; α7nAChR