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Genome-Wide Analysis of Menin Binding Provides Insights into MEN1 Tumorigenesis
Multiple endocrine neoplasia type I (MEN1) is a familial cancer syndrome characterized primarily by tumors of multiple endocrine glands. The gene for MEN1 encodes a ubiquitously expressed tumor suppressor protein called menin. Menin was recently shown to interact with several components of a trithor...
Autores principales: | , , , , , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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Public Library of Science
2006
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1428788/ https://www.ncbi.nlm.nih.gov/pubmed/16604156 http://dx.doi.org/10.1371/journal.pgen.0020051 |
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author | Scacheri, Peter C Davis, Sean Odom, Duncan T Crawford, Gregory E Perkins, Stacie Halawi, Mohamad J Agarwal, Sunita K Marx, Stephen J Spiegel, Allen M Meltzer, Paul S Collins, Francis S |
author_facet | Scacheri, Peter C Davis, Sean Odom, Duncan T Crawford, Gregory E Perkins, Stacie Halawi, Mohamad J Agarwal, Sunita K Marx, Stephen J Spiegel, Allen M Meltzer, Paul S Collins, Francis S |
author_sort | Scacheri, Peter C |
collection | PubMed |
description | Multiple endocrine neoplasia type I (MEN1) is a familial cancer syndrome characterized primarily by tumors of multiple endocrine glands. The gene for MEN1 encodes a ubiquitously expressed tumor suppressor protein called menin. Menin was recently shown to interact with several components of a trithorax family histone methyltransferase complex including ASH2, Rbbp5, WDR5, and the leukemia proto-oncoprotein MLL. To elucidate menin's role as a tumor suppressor and gain insights into the endocrine-specific tumor phenotype in MEN1, we mapped the genomic binding sites of menin, MLL1, and Rbbp5, to approximately 20,000 promoters in HeLa S3, HepG2, and pancreatic islet cells using the strategy of chromatin-immunoprecipitation coupled with microarray analysis. We found that menin, MLL1, and Rbbp5 localize to the promoters of thousands of human genes but do not always bind together. These data suggest that menin functions as a general regulator of transcription. We also found that factor occupancy generally correlates with high gene expression but that the loss of menin does not result in significant changes in most transcript levels. One exception is the developmentally programmed transcription factor, HLXB9, which is overexpressed in islets in the absence of menin. Our findings expand the realm of menin-targeted genes several hundred-fold beyond that previously described and provide potential insights to the endocrine tumor bias observed in MEN1 patients. |
format | Text |
id | pubmed-1428788 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2006 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-14287882006-05-08 Genome-Wide Analysis of Menin Binding Provides Insights into MEN1 Tumorigenesis Scacheri, Peter C Davis, Sean Odom, Duncan T Crawford, Gregory E Perkins, Stacie Halawi, Mohamad J Agarwal, Sunita K Marx, Stephen J Spiegel, Allen M Meltzer, Paul S Collins, Francis S PLoS Genet Research Article Multiple endocrine neoplasia type I (MEN1) is a familial cancer syndrome characterized primarily by tumors of multiple endocrine glands. The gene for MEN1 encodes a ubiquitously expressed tumor suppressor protein called menin. Menin was recently shown to interact with several components of a trithorax family histone methyltransferase complex including ASH2, Rbbp5, WDR5, and the leukemia proto-oncoprotein MLL. To elucidate menin's role as a tumor suppressor and gain insights into the endocrine-specific tumor phenotype in MEN1, we mapped the genomic binding sites of menin, MLL1, and Rbbp5, to approximately 20,000 promoters in HeLa S3, HepG2, and pancreatic islet cells using the strategy of chromatin-immunoprecipitation coupled with microarray analysis. We found that menin, MLL1, and Rbbp5 localize to the promoters of thousands of human genes but do not always bind together. These data suggest that menin functions as a general regulator of transcription. We also found that factor occupancy generally correlates with high gene expression but that the loss of menin does not result in significant changes in most transcript levels. One exception is the developmentally programmed transcription factor, HLXB9, which is overexpressed in islets in the absence of menin. Our findings expand the realm of menin-targeted genes several hundred-fold beyond that previously described and provide potential insights to the endocrine tumor bias observed in MEN1 patients. Public Library of Science 2006-04 2006-04-07 /pmc/articles/PMC1428788/ /pubmed/16604156 http://dx.doi.org/10.1371/journal.pgen.0020051 Text en This is an open-access article distributed under the terms of the Creative Commons Public Domain declaration which stipulates that, once placed in the public domain, this work may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. https://creativecommons.org/publicdomain/zero/1.0/ This is an open-access article distributed under the terms of the Creative Commons Public Domain declaration, which stipulates that, once placed in the public domain, this work may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. |
spellingShingle | Research Article Scacheri, Peter C Davis, Sean Odom, Duncan T Crawford, Gregory E Perkins, Stacie Halawi, Mohamad J Agarwal, Sunita K Marx, Stephen J Spiegel, Allen M Meltzer, Paul S Collins, Francis S Genome-Wide Analysis of Menin Binding Provides Insights into MEN1 Tumorigenesis |
title | Genome-Wide Analysis of Menin Binding Provides Insights into MEN1 Tumorigenesis |
title_full | Genome-Wide Analysis of Menin Binding Provides Insights into MEN1 Tumorigenesis |
title_fullStr | Genome-Wide Analysis of Menin Binding Provides Insights into MEN1 Tumorigenesis |
title_full_unstemmed | Genome-Wide Analysis of Menin Binding Provides Insights into MEN1 Tumorigenesis |
title_short | Genome-Wide Analysis of Menin Binding Provides Insights into MEN1 Tumorigenesis |
title_sort | genome-wide analysis of menin binding provides insights into men1 tumorigenesis |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1428788/ https://www.ncbi.nlm.nih.gov/pubmed/16604156 http://dx.doi.org/10.1371/journal.pgen.0020051 |
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