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Identification of two regulatory binding sites which confer myotube specific expression of the mono-ADP-ribosyltransferase ART1 gene
BACKGROUND: Mono-ADP-ribosyltransferase (ART) 1 belongs to a family of mammalian ectoenzymes that catalyze the transfer of ADP-ribose from NAD(+ )to a target protein. ART1 is predominantly expressed in skeletal and cardiac muscle. It ADP-ribosylates α7-integrin which together with β1-integrin forms...
Autores principales: | , , , , |
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Formato: | Texto |
Lenguaje: | English |
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BioMed Central
2008
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2575215/ https://www.ncbi.nlm.nih.gov/pubmed/18939989 http://dx.doi.org/10.1186/1471-2199-9-91 |
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author | Friedrich, Maik Böhlig, Levin Kirschner, Ralf D Engeland, Kurt Hauschildt, Sunna |
author_facet | Friedrich, Maik Böhlig, Levin Kirschner, Ralf D Engeland, Kurt Hauschildt, Sunna |
author_sort | Friedrich, Maik |
collection | PubMed |
description | BACKGROUND: Mono-ADP-ribosyltransferase (ART) 1 belongs to a family of mammalian ectoenzymes that catalyze the transfer of ADP-ribose from NAD(+ )to a target protein. ART1 is predominantly expressed in skeletal and cardiac muscle. It ADP-ribosylates α7-integrin which together with β1-integrin forms a dimer and binds to laminin, a protein of the extracellular matrix involved in cell adhesion. This posttranslational modification leads to an increased laminin binding affinity. RESULTS: Using C2C12 and C3H-10T 1/2 cells as models of myogenesis, we found that ART1 expression was restricted to myotube formation. We identified a fragment spanning the gene 1.3 kb upstream of the transcriptional start site as the functional promoter of the ART1 gene. This region contains an E box and an A/T-rich element, two conserved binding sites for transcription factors found in the promoters of most skeletal muscle specific genes. Mutating the DNA consensus sequence of either the E box or the A/T-rich element resulted in a nearly complete loss of ART1 promoter inducibility, indicating a cooperative role of the transcription factors binding to those sites. Gel mobility shift analyses carried out with nuclear extracts from C2C12 and C3H-10T 1/2 cells revealed binding of myogenin to the E box and MEF-2 to the A/T-rich element, the binding being restricted to C2C12 and C3H-10T 1/2 myotubes. CONCLUSION: Here we describe the molecular mechanism underlying the regulation of the ART1 gene expression in skeletal muscle cells. The differentiation-dependent upregulation of ART1 mRNA is induced by the binding of myogenin to an E box and of MEF-2 to an A/T-rich element in the proximal promoter region of the ART1 gene. Thus the transcriptional regulation involves molecular mechanisms similar to those used to activate muscle-specific genes. |
format | Text |
id | pubmed-2575215 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2008 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-25752152008-10-30 Identification of two regulatory binding sites which confer myotube specific expression of the mono-ADP-ribosyltransferase ART1 gene Friedrich, Maik Böhlig, Levin Kirschner, Ralf D Engeland, Kurt Hauschildt, Sunna BMC Mol Biol Research Article BACKGROUND: Mono-ADP-ribosyltransferase (ART) 1 belongs to a family of mammalian ectoenzymes that catalyze the transfer of ADP-ribose from NAD(+ )to a target protein. ART1 is predominantly expressed in skeletal and cardiac muscle. It ADP-ribosylates α7-integrin which together with β1-integrin forms a dimer and binds to laminin, a protein of the extracellular matrix involved in cell adhesion. This posttranslational modification leads to an increased laminin binding affinity. RESULTS: Using C2C12 and C3H-10T 1/2 cells as models of myogenesis, we found that ART1 expression was restricted to myotube formation. We identified a fragment spanning the gene 1.3 kb upstream of the transcriptional start site as the functional promoter of the ART1 gene. This region contains an E box and an A/T-rich element, two conserved binding sites for transcription factors found in the promoters of most skeletal muscle specific genes. Mutating the DNA consensus sequence of either the E box or the A/T-rich element resulted in a nearly complete loss of ART1 promoter inducibility, indicating a cooperative role of the transcription factors binding to those sites. Gel mobility shift analyses carried out with nuclear extracts from C2C12 and C3H-10T 1/2 cells revealed binding of myogenin to the E box and MEF-2 to the A/T-rich element, the binding being restricted to C2C12 and C3H-10T 1/2 myotubes. CONCLUSION: Here we describe the molecular mechanism underlying the regulation of the ART1 gene expression in skeletal muscle cells. The differentiation-dependent upregulation of ART1 mRNA is induced by the binding of myogenin to an E box and of MEF-2 to an A/T-rich element in the proximal promoter region of the ART1 gene. Thus the transcriptional regulation involves molecular mechanisms similar to those used to activate muscle-specific genes. BioMed Central 2008-10-21 /pmc/articles/PMC2575215/ /pubmed/18939989 http://dx.doi.org/10.1186/1471-2199-9-91 Text en Copyright © 2008 Friedrich et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( (http://creativecommons.org/licenses/by/2.0) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Article Friedrich, Maik Böhlig, Levin Kirschner, Ralf D Engeland, Kurt Hauschildt, Sunna Identification of two regulatory binding sites which confer myotube specific expression of the mono-ADP-ribosyltransferase ART1 gene |
title | Identification of two regulatory binding sites which confer myotube specific expression of the mono-ADP-ribosyltransferase ART1 gene |
title_full | Identification of two regulatory binding sites which confer myotube specific expression of the mono-ADP-ribosyltransferase ART1 gene |
title_fullStr | Identification of two regulatory binding sites which confer myotube specific expression of the mono-ADP-ribosyltransferase ART1 gene |
title_full_unstemmed | Identification of two regulatory binding sites which confer myotube specific expression of the mono-ADP-ribosyltransferase ART1 gene |
title_short | Identification of two regulatory binding sites which confer myotube specific expression of the mono-ADP-ribosyltransferase ART1 gene |
title_sort | identification of two regulatory binding sites which confer myotube specific expression of the mono-adp-ribosyltransferase art1 gene |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2575215/ https://www.ncbi.nlm.nih.gov/pubmed/18939989 http://dx.doi.org/10.1186/1471-2199-9-91 |
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