Discovering Transcription and Splicing Networks in Myelodysplastic Syndromes

More and more transcription factors and their motifs have been reported and linked to specific gene expression levels. However, focusing only on transcription is not sufficient for mechanism research. Most genes, especially in eukaryotes, are alternatively spliced to different isoforms. Some of thes...

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Autores principales: Wang, Hongyan, Wen, Jianguo, Chang, Chung-che, Zhou, Xiaobo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3828332/
https://www.ncbi.nlm.nih.gov/pubmed/24244432
http://dx.doi.org/10.1371/journal.pone.0079118
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author Wang, Hongyan
Wen, Jianguo
Chang, Chung-che
Zhou, Xiaobo
author_facet Wang, Hongyan
Wen, Jianguo
Chang, Chung-che
Zhou, Xiaobo
author_sort Wang, Hongyan
collection PubMed
description More and more transcription factors and their motifs have been reported and linked to specific gene expression levels. However, focusing only on transcription is not sufficient for mechanism research. Most genes, especially in eukaryotes, are alternatively spliced to different isoforms. Some of these isoforms increase the biodiversity of proteins. From this viewpoint, transcription and splicing are two of important mechanisms to modulate expression levels of isoforms. To integrate these two kinds of regulation, we built a linear regression model to select a subset of transcription factors and splicing factors for each co-expressed isoforms using least-angle regression approach. Then, we applied this method to investigate the mechanism of myelodysplastic syndromes (MDS), a precursor lesion of acute myeloid leukemia. Results suggested that expression levels of most isoforms were regulated by a set of selected regulatory factors. Some of the detected factors, such as EGR1 and STAT family, are highly correlated with progression of MDS. We discovered that the splicing factor SRSF11 experienced alternative splicing switch, and in turn induced different amino acid sequences between MDS and controls. This splicing switch causes two different splicing mechanisms. Polymerase Chain Reaction experiments also confirmed that one of its isoforms was over-expressed in MDS. We analyzed the regulatory networks constructed from the co-expressed isoforms and their regulatory factors in MDS. Many of these networks were enriched in the herpes simplex infection pathway which involves many splicing factors, and pathways in cancers and acute or chronic myeloid leukemia.
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spelling pubmed-38283322013-11-16 Discovering Transcription and Splicing Networks in Myelodysplastic Syndromes Wang, Hongyan Wen, Jianguo Chang, Chung-che Zhou, Xiaobo PLoS One Research Article More and more transcription factors and their motifs have been reported and linked to specific gene expression levels. However, focusing only on transcription is not sufficient for mechanism research. Most genes, especially in eukaryotes, are alternatively spliced to different isoforms. Some of these isoforms increase the biodiversity of proteins. From this viewpoint, transcription and splicing are two of important mechanisms to modulate expression levels of isoforms. To integrate these two kinds of regulation, we built a linear regression model to select a subset of transcription factors and splicing factors for each co-expressed isoforms using least-angle regression approach. Then, we applied this method to investigate the mechanism of myelodysplastic syndromes (MDS), a precursor lesion of acute myeloid leukemia. Results suggested that expression levels of most isoforms were regulated by a set of selected regulatory factors. Some of the detected factors, such as EGR1 and STAT family, are highly correlated with progression of MDS. We discovered that the splicing factor SRSF11 experienced alternative splicing switch, and in turn induced different amino acid sequences between MDS and controls. This splicing switch causes two different splicing mechanisms. Polymerase Chain Reaction experiments also confirmed that one of its isoforms was over-expressed in MDS. We analyzed the regulatory networks constructed from the co-expressed isoforms and their regulatory factors in MDS. Many of these networks were enriched in the herpes simplex infection pathway which involves many splicing factors, and pathways in cancers and acute or chronic myeloid leukemia. Public Library of Science 2013-11-14 /pmc/articles/PMC3828332/ /pubmed/24244432 http://dx.doi.org/10.1371/journal.pone.0079118 Text en © 2013 Wang 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
Wang, Hongyan
Wen, Jianguo
Chang, Chung-che
Zhou, Xiaobo
Discovering Transcription and Splicing Networks in Myelodysplastic Syndromes
title Discovering Transcription and Splicing Networks in Myelodysplastic Syndromes
title_full Discovering Transcription and Splicing Networks in Myelodysplastic Syndromes
title_fullStr Discovering Transcription and Splicing Networks in Myelodysplastic Syndromes
title_full_unstemmed Discovering Transcription and Splicing Networks in Myelodysplastic Syndromes
title_short Discovering Transcription and Splicing Networks in Myelodysplastic Syndromes
title_sort discovering transcription and splicing networks in myelodysplastic syndromes
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3828332/
https://www.ncbi.nlm.nih.gov/pubmed/24244432
http://dx.doi.org/10.1371/journal.pone.0079118
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