Transcriptional regulation of the Alström syndrome gene ALMS1 by members of the RFX family and Sp1
Transcriptional regulation of the Alström syndrome gene ALMS1 by members of the RFX family and Sp1
Mutations in the human gene ALMS1 cause Alström syndrome, a disorder characterised by neurosensory degeneration, metabolic defects and cardiomyopathy. ALMS1 encodes a centrosomal protein implicated in the assembly and maintenance of primary cilia. Expression of ALMS1 varies between tissues and recent data suggest that its transcription is modulated during adipogenesis and growth arrest. However the ALMS1 promoter has not been defined. This study focused on identifying and characterising the ALMS1 proximal promoter, initially by using 5' RACE to map transcription start sites. Luciferase reporter assay and EMSA data strongly suggest that ALMS1 transcription is regulated by the ubiquitous factor Sp1. In addition, reporter assay, EMSA, chromatin immunoprecipitation and RNA interference data indicate that ALMS1 transcription is regulated by regulatory factor X (RFX) proteins. These transcription factors are cell-type restricted in their expression profile and known to regulate genes of the ciliogenic pathway. We show binding of RFX proteins to an evolutionarily conserved X-box in the ALMS1 proximal promoter and present evidence that these proteins are responsible for ALMS1 transcription during growth arrest induced by low serum conditions. In summary, this work provides the first data on transcription factors regulating general and context-specific transcription of the disease-associated gene ALMS1
transcription, promoter, X-box, GC-box, cilia
20-29
Purvis, Tracey L.
a2941cc1-e316-42ea-a24a-c6395b701ec6
Hearn, Tom
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Spalluto, Cosma
6802ad50-bc38-404f-9a19-40916425183b
Knorz, Victoria J.
f0084ead-54c9-4885-b60e-9360dcf3d524
Piper Hanley, Karen
f11a1076-ad7d-446e-bd59-96814475e06f
Sanchez-Elsner, Tilman
b8799f8d-e2b4-4b37-b77c-f2f0e8e2070d
Hanley, Neil A.
bf03f7bb-f377-44fb-8344-0bb1ca8b2ef9
Wilson, David I.
1500fca1-7082-4271-95f4-691f1d1252a2
15 July 2010
Purvis, Tracey L.
a2941cc1-e316-42ea-a24a-c6395b701ec6
Hearn, Tom
2665cc10-6632-47cb-9460-bd0ea745380e
Spalluto, Cosma
6802ad50-bc38-404f-9a19-40916425183b
Knorz, Victoria J.
f0084ead-54c9-4885-b60e-9360dcf3d524
Piper Hanley, Karen
f11a1076-ad7d-446e-bd59-96814475e06f
Sanchez-Elsner, Tilman
b8799f8d-e2b4-4b37-b77c-f2f0e8e2070d
Hanley, Neil A.
bf03f7bb-f377-44fb-8344-0bb1ca8b2ef9
Wilson, David I.
1500fca1-7082-4271-95f4-691f1d1252a2
Purvis, Tracey L., Hearn, Tom, Spalluto, Cosma, Knorz, Victoria J., Piper Hanley, Karen, Sanchez-Elsner, Tilman, Hanley, Neil A. and Wilson, David I.
(2010)
Transcriptional regulation of the Alström syndrome gene ALMS1 by members of the RFX family and Sp1.
Gene, 460 (1-2), .
(doi:10.1016/j.gene.2010.03.015).
Abstract
Mutations in the human gene ALMS1 cause Alström syndrome, a disorder characterised by neurosensory degeneration, metabolic defects and cardiomyopathy. ALMS1 encodes a centrosomal protein implicated in the assembly and maintenance of primary cilia. Expression of ALMS1 varies between tissues and recent data suggest that its transcription is modulated during adipogenesis and growth arrest. However the ALMS1 promoter has not been defined. This study focused on identifying and characterising the ALMS1 proximal promoter, initially by using 5' RACE to map transcription start sites. Luciferase reporter assay and EMSA data strongly suggest that ALMS1 transcription is regulated by the ubiquitous factor Sp1. In addition, reporter assay, EMSA, chromatin immunoprecipitation and RNA interference data indicate that ALMS1 transcription is regulated by regulatory factor X (RFX) proteins. These transcription factors are cell-type restricted in their expression profile and known to regulate genes of the ciliogenic pathway. We show binding of RFX proteins to an evolutionarily conserved X-box in the ALMS1 proximal promoter and present evidence that these proteins are responsible for ALMS1 transcription during growth arrest induced by low serum conditions. In summary, this work provides the first data on transcription factors regulating general and context-specific transcription of the disease-associated gene ALMS1
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Accepted/In Press date: 7 April 2010
Published date: 15 July 2010
Keywords:
transcription, promoter, X-box, GC-box, cilia
Organisations:
Human Genetics, Infection Inflammation & Immunity
Identifiers
Local EPrints ID: 143849
URI: http://eprints.soton.ac.uk/id/eprint/143849
ISSN: 0378-1119
PURE UUID: 7e371a3e-7a7c-40c6-a907-39ccf37610e3
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Date deposited: 13 Apr 2010 12:48
Last modified: 14 Mar 2024 02:53
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Contributors
Author:
Tracey L. Purvis
Author:
Tom Hearn
Author:
Cosma Spalluto
Author:
Victoria J. Knorz
Author:
Karen Piper Hanley
Author:
Neil A. Hanley
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