Evolutionary silencing of the human elastase I gene (ELA1)

Human Molecular Genetics
S D Rose, R J MacDonald

Abstract

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 pr...Continue Reading

References

Jan 1, 1992·DNA Sequence : the Journal of DNA Sequencing and Mapping·I KawashimaY Takiguchi
Dec 1, 1991·Molecular and Cellular Biology·K MonicaM L Cleary
Jun 1, 1986·Proceedings of the National Academy of Sciences of the United States of America·A M BouletW J Rutter
Jan 1, 1987·Methods in Enzymology·T A KunkelR A Zakour
Feb 1, 1988·Molecular and Cellular Biology·F KruseR J MacDonald
Apr 1, 1973·Virology·F L Graham, A J van der Eb
Sep 26, 1995·Proceedings of the National Academy of Sciences of the United States of America·S T NeuteboomC Murre
Aug 1, 1995·Molecular and Cellular Biology·M L PhelanM S Featherstone
Aug 1, 1995·Molecular and Cellular Biology·F KruseR J MacDonald

❮ Previous
Next ❯

Citations

Jan 6, 2007·Digestive Diseases and Sciences·David C Whitcomb, Mark E Lowe
Apr 3, 2004·Genome Research·Xose S Puente, Carlos López-Otín
Feb 14, 2003·Evolution; International Journal of Organic Evolution·Marcelo D CorteseEsteban Hasson
Apr 3, 2002·Evolution; International Journal of Organic Evolution·Fabian M Norry, Volker Loeschcke
Apr 3, 2002·Evolution; International Journal of Organic Evolution·Urs Kraushaar, Wolf U Blanckenhorn
May 7, 2002·Evolution; International Journal of Organic Evolution·Kenneth M Fedorka, Timothy A Mousseau
May 7, 2002·Evolution; International Journal of Organic Evolution·Anssi LaurilaJuha Merilä
Oct 2, 2002·Evolution; International Journal of Organic Evolution·E B KruukTim Clutton-Brock
Sep 11, 2009·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·David M MeredithJane E Johnson
Aug 27, 2015·Diabetes·Dagmar KleinJuan Domínguez-Bendala
Jan 18, 2016·Annals of Allergy, Asthma & Immunology : Official Publication of the American College of Allergy, Asthma, & Immunology·David González-de-OlanoCarlos Pastor-Vargas
Oct 7, 2006·Human Mutation·Hildegard Kehrer-Sawatzki, David N Cooper
Oct 28, 2008·The Anatomical Record : Advances in Integrative Anatomy and Evolutionary Biology·Samuel MárquezSteven D Schaefer
Dec 6, 2005·Pancreatology : Official Journal of the International Association of Pancreatology (IAP) ... [et Al.]·Edit Szepessy, Miklós Sahin-Tóth
Jul 28, 2016·PloS One·Frank Ulrich WeissMarkus M Lerch
Dec 14, 2017·Genes·Anna Tracewska-SiemiątkowskaLisbeth Tranebjærg
Apr 1, 2017·American Journal of Physiology. Gastrointestinal and Liver Physiology·Anna Zsófia TóthMiklós Sahin-Tóth
Jul 3, 2003·Nature Reviews. Genetics·Xose S PuenteCarlos López-Otín
Sep 20, 2001·The Journal of Biological Chemistry·S D RoseR J MacDonald
Mar 21, 2017·Digestive Diseases and Sciences·J Enrique Domínguez-MuñozMatthias J Löhr
Dec 12, 2019·F1000Research·Yaseen Perbtani, Chris E Forsmark
Nov 25, 2018·Cellular and Molecular Life Sciences : CMLS·Kangxin Jin, Mengqing Xiang
Jul 1, 2016·The Journal of Biological Chemistry·András SzabóMiklós Sahin-Tóth

❮ Previous
Next ❯

Related Concepts

Related Feeds

CREs: Gene & Cell Therapy

Gene and cell therapy advances have shown promising outcomes for several diseases. The role of cis-regulatory elements (CREs) is crucial in the design of gene therapy vectors. Here is the latest research on CREs in gene and cell therapy.