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Dosage Regulation of the Active X Chromosome in Human Triploid Cells
In mammals, dosage compensation is achieved by doubling expression of X-linked genes in both sexes, together with X inactivation in females. Up-regulation of the active X chromosome may be controlled by DNA sequence–based and/or epigenetic mechanisms that double the X output potentially in response...
Autores principales: | , , , , , |
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Formato: | Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2009
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2777382/ https://www.ncbi.nlm.nih.gov/pubmed/19997486 http://dx.doi.org/10.1371/journal.pgen.1000751 |
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author | Deng, Xinxian Nguyen, Di Kim Hansen, R. Scott Van Dyke, Daniel L. Gartler, Stanley M. Disteche, Christine M. |
author_facet | Deng, Xinxian Nguyen, Di Kim Hansen, R. Scott Van Dyke, Daniel L. Gartler, Stanley M. Disteche, Christine M. |
author_sort | Deng, Xinxian |
collection | PubMed |
description | In mammals, dosage compensation is achieved by doubling expression of X-linked genes in both sexes, together with X inactivation in females. Up-regulation of the active X chromosome may be controlled by DNA sequence–based and/or epigenetic mechanisms that double the X output potentially in response to autosomal factor(s). To determine whether X expression is adjusted depending on ploidy, we used expression arrays to compare X-linked and autosomal gene expression in human triploid cells. While the average X:autosome expression ratio was about 1 in normal diploid cells, this ratio was lower (0.81–0.84) in triploid cells with one active X and higher (1.32–1.4) in triploid cells with two active X's. Thus, overall X-linked gene expression in triploid cells does not strictly respond to an autosomal factor, nor is it adjusted to achieve a perfect balance. The unbalanced X:autosome expression ratios that we observed could contribute to the abnormal phenotypes associated with triploidy. Absolute autosomal expression levels per gene copy were similar in triploid versus diploid cells, indicating no apparent global effect on autosomal expression. In triploid cells with two active X's our data support a basic doubling of X-linked gene expression. However, in triploid cells with a single active X, X-linked gene expression is adjusted upward presumably by an epigenetic mechanism that senses the ratio between the number of active X chromosomes and autosomal sets. Such a mechanism may act on a subset of genes whose expression dosage in relation to autosomal expression may be critical. Indeed, we found that there was a range of individual X-linked gene expression in relation to ploidy and that a small subset (∼7%) of genes had expression levels apparently proportional to the number of autosomal sets. |
format | Text |
id | pubmed-2777382 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2009 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-27773822009-12-08 Dosage Regulation of the Active X Chromosome in Human Triploid Cells Deng, Xinxian Nguyen, Di Kim Hansen, R. Scott Van Dyke, Daniel L. Gartler, Stanley M. Disteche, Christine M. PLoS Genet Research Article In mammals, dosage compensation is achieved by doubling expression of X-linked genes in both sexes, together with X inactivation in females. Up-regulation of the active X chromosome may be controlled by DNA sequence–based and/or epigenetic mechanisms that double the X output potentially in response to autosomal factor(s). To determine whether X expression is adjusted depending on ploidy, we used expression arrays to compare X-linked and autosomal gene expression in human triploid cells. While the average X:autosome expression ratio was about 1 in normal diploid cells, this ratio was lower (0.81–0.84) in triploid cells with one active X and higher (1.32–1.4) in triploid cells with two active X's. Thus, overall X-linked gene expression in triploid cells does not strictly respond to an autosomal factor, nor is it adjusted to achieve a perfect balance. The unbalanced X:autosome expression ratios that we observed could contribute to the abnormal phenotypes associated with triploidy. Absolute autosomal expression levels per gene copy were similar in triploid versus diploid cells, indicating no apparent global effect on autosomal expression. In triploid cells with two active X's our data support a basic doubling of X-linked gene expression. However, in triploid cells with a single active X, X-linked gene expression is adjusted upward presumably by an epigenetic mechanism that senses the ratio between the number of active X chromosomes and autosomal sets. Such a mechanism may act on a subset of genes whose expression dosage in relation to autosomal expression may be critical. Indeed, we found that there was a range of individual X-linked gene expression in relation to ploidy and that a small subset (∼7%) of genes had expression levels apparently proportional to the number of autosomal sets. Public Library of Science 2009-12-04 /pmc/articles/PMC2777382/ /pubmed/19997486 http://dx.doi.org/10.1371/journal.pgen.1000751 Text en Deng et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Deng, Xinxian Nguyen, Di Kim Hansen, R. Scott Van Dyke, Daniel L. Gartler, Stanley M. Disteche, Christine M. Dosage Regulation of the Active X Chromosome in Human Triploid Cells |
title | Dosage Regulation of the Active X Chromosome in Human Triploid Cells |
title_full | Dosage Regulation of the Active X Chromosome in Human Triploid Cells |
title_fullStr | Dosage Regulation of the Active X Chromosome in Human Triploid Cells |
title_full_unstemmed | Dosage Regulation of the Active X Chromosome in Human Triploid Cells |
title_short | Dosage Regulation of the Active X Chromosome in Human Triploid Cells |
title_sort | dosage regulation of the active x chromosome in human triploid cells |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2777382/ https://www.ncbi.nlm.nih.gov/pubmed/19997486 http://dx.doi.org/10.1371/journal.pgen.1000751 |
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