Human Molecular Genetics, Vol 6, 897-903, Copyright © 1997 by Oxford University Press
SD Rose and RJ MacDonald
The human pancreatic elastase I gene is transcriptionally silent, despite
the apparent integrity of the structural gene. The transcriptional
regulatory sequences necessary and sufficient for transcription of the
active rat homologue are localized within 205 base pairs (bp) of the
transcriptional start and comprise a pancreas- specific transcriptional
enhancer of 134 bp immediately upstream of a 71 bp non-specific promoter.
The human gene has 58 nucleotide differences within this region, 13 of
which are in the three functional elements (A, B and C) that constitute the
enhancer. Through cell transfection analyses with a pancreatic acinar tumor
cell line, we show that the nucleotide differences in the human 5' flanking
gene sequences have inactivated both the enhancer and the promoter. The
changes in the three elements of the human enhancer alone are sufficient to
inactivate the enhancer; conversely, restoring these to the rat
configuration partially restores the activity of the human enhancer. The
two mutations in the A element and the four mutations in the B element
abolish the binding of the transcription factors previously shown to
mediate the activity of these elements. Replacing the active 71 bp rat
promoter with the human promoter also prevents expression. Therefore, the
evolutionary silencing of the human elastase I gene appears due to
mutations that inactivate crucial enhancer and promoter elements.
ARTICLES
Evolutionary silencing of the human elastase I gene (ELA1)
Department of Molecular Biology and Oncology, University of Texas Southwestern Medical Center, Dallas 75235-9140, USA.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  D. M. Meredith, T. Masui, G. H. Swift, R. J. MacDonald, and J. E. Johnson Multiple Transcriptional Mechanisms Control Ptf1a Levels during Neural Development Including Autoregulation by the PTF1-J Complex J. Neurosci., September 9, 2009; 29(36): 11139 - 11148. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Masui, Q. Long, T. M. Beres, M. A. Magnuson, and R. J. MacDonald Early pancreatic development requires the vertebrate Suppressor of Hairless (RBPJ) in the PTF1 bHLH complex Genes & Dev., October 15, 2007; 21(20): 2629 - 2643. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. E. Schienman, R. A. Holt, M. R. Auerbach, and C.-B. Stewart Duplication and Divergence of 2 Distinct Pancreatic Ribonuclease Genes in Leaf-Eating African and Asian Colobine Monkeys Mol. Biol. Evol., August 1, 2006; 23(8): 1465 - 1479. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. M. Beres, T. Masui, G. H. Swift, L. Shi, R. M. Henke, and R. J. MacDonald PTF1 Is an Organ-Specific and Notch-Independent Basic Helix-Loop-Helix Complex Containing the Mammalian Suppressor of Hairless (RBP-J) or Its Paralogue, RBP-L Mol. Cell. Biol., January 1, 2006; 26(1): 117 - 130. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 X. S. Puente and C. Lopez-Otin A Genomic Analysis of Rat Proteases and Protease Inhibitors Genome Res., April 1, 2004; 14(4): 609 - 622. [Abstract] [Full Text] [PDF]
|
|