Use of transgenic mice to map cis-acting elements in the intestinal fatty acid binding protein gene (Fabpi) that control its cell lineage- specific and regional patterns of expression along the duodenal-colonic and crypt-villus axes of the gut epithelium
| العنوان: | Use of transgenic mice to map cis-acting elements in the intestinal fatty acid binding protein gene (Fabpi) that control its cell lineage- specific and regional patterns of expression along the duodenal-colonic and crypt-villus axes of the gut epithelium |
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| المؤلفون: | Steven M. Cohn, Kevin A. Roth, E H Birkenmeier, T. C. Simon, Jeffrey I. Gordon |
| المصدر: | The Journal of Cell Biology |
| بيانات النشر: | The Rockefeller University Press, 1992. |
| سنة النشر: | 1992 |
| مصطلحات موضوعية: | Colon, Duodenum, Recombinant Fusion Proteins, Crypt, Molecular Sequence Data, Fluorescent Antibody Technique, Mice, Transgenic, Nerve Tissue Proteins, Biology, Regulatory Sequences, Nucleic Acid, Fatty Acid-Binding Proteins, Epithelium, Mice, Intestinal mucosa, Enhancer binding, Gene expression, medicine, Animals, Intestinal Mucosa, Regulation of gene expression, Base Sequence, Fatty Acids, Nuclear Proteins, Cell Biology, Articles, Blotting, Northern, Molecular biology, Intestinal epithelium, Neoplasm Proteins, DNA-Binding Proteins, medicine.anatomical_structure, Gene Expression Regulation, Regulatory sequence, Growth Hormone, Paneth cell, CCAAT-Enhancer-Binding Proteins, Carrier Proteins, Fatty Acid-Binding Protein 7, Transcription Factors |
| الوصف: | The mouse intestinal epithelium is able to establish and maintain complex lineage-specific, spatial, and temporal patterns of gene expression despite its rapid and continuous renewal. A multipotent stem cell located near the base of each intestinal crypt gives rise to progeny which undergo amplification and allocation to either enterocytic, Paneth cell, goblet cell, or enteroendocrine cell lineages. Differentiation of these four lineages occurs during their geographically ordered migration along the crypt-villus axis. Gut stem cells appear to have a "positional address" which is manifested by differences in the differentiation programs of their lineal descendants along the duodenal-colonic (cephalocaudal) axis. We have used the intestinal fatty acid binding protein gene (Fabpi) as a model to identify cis-acting elements which regulate cell- and region-specific patterns of gene expression in the gut. Nucleotides -1178 to +28 of rat Fabpi direct a pattern of expression of a reporter (human growth hormone [hGH]) which mimics that of mouse Fabpi (a) steady-state levels of hGH mRNA are highest in the distal jejunum of adult transgenic mice and fall progressively toward both the duodenum and the mid-colon; and (b) hGH is confined to the enterocytic lineage and first appears as postmitotic, differentiating cells exit the crypt and migrate to the base of small intestinal villi or their colonic homologs, the surface epithelial cuffs. Nucleotides -103 to +28, which are highly conserved in rat, mouse and human Fabpi, are able to correctly initiate transgene expression in late fetal life, restrict hGH to the enterocytic lineage, and establish an appropriate cephalocaudal gradient of reporter expression. This cephalocaudal gradient is also influenced by cis-acting elements located between nucleotides -1178 and -278, and -277 and -185 that enhance and suppress (respectively) expression in the ileum and colon and by element(s) located upstream of nucleotide -277 that are needed to sustain high levels of hGH production after weaning. Nucleotides -277 to -185 contain part of a domain conserved between the three orthologous Fabpi genes (nucleotides -240 to -159), a 24-bp element (nucleotides -212 to -188) that binds nuclear factors present in colonic but not small intestinal epithelial cells, and a portion of a CCAAT/enhancer binding protein footprint (C/EBP alpha, nucleotides -188 to -167). Removal of nucleotides -277 to -185 (yielding I-FABP-184 to +28/hGH+3) results in inappropriate expression of hGH in proliferating and nonproliferating epithelial cells located in the mid and upper portions of duodenal, jejunal, ileal, and colonic crypts without affecting the "shape" of the cephalocaudal gradient of transgene expression.(ABSTRACT TRUNCATED AT 400 WORDS) |
| اللغة: | English |
| تدمد: | 1540-8140 0021-9525 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::a97a2b3ae338cebe770a9a643712cf96Test http://europepmc.org/articles/PMC2289640Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....a97a2b3ae338cebe770a9a643712cf96 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15408140 00219525 |
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