Integrated transcription factor profiling with transcriptome analysis identifies L1PA2 transposons as global regulatory modulators in a breast cancer model

Abstract While transposons are generally silenced in somatic tissues, many transposons escape epigenetic repression in epithelial cancers, become transcriptionally active and contribute to the regulation of human gene expression. We have developed a bioinformatic pipeline for the integrated analysis...

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Autores principales:	Jiayue-Clara Jiang, Joseph A. Rothnagel, Kyle R. Upton
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/b7fc12492b4b4d2bb4b821a58664062c
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spelling	oai:doaj.org-article:b7fc12492b4b4d2bb4b821a58664062c2021-12-02T14:26:25ZIntegrated transcription factor profiling with transcriptome analysis identifies L1PA2 transposons as global regulatory modulators in a breast cancer model10.1038/s41598-021-86395-92045-2322https://doaj.org/article/b7fc12492b4b4d2bb4b821a58664062c2021-04-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-86395-9https://doaj.org/toc/2045-2322Abstract While transposons are generally silenced in somatic tissues, many transposons escape epigenetic repression in epithelial cancers, become transcriptionally active and contribute to the regulation of human gene expression. We have developed a bioinformatic pipeline for the integrated analysis of transcription factor binding and transcriptomic data to identify transposon-derived promoters that are activated in specific diseases and developmental states. We applied this pipeline to a breast cancer model, and found that the L1PA2 transposon subfamily contributes abundant regulatory sequences to co-ordinated transcriptional regulation in breast cancer. Transcription factor profiling demonstrates that over 27% of L1PA2 transposons harbour co-localised binding sites of functionally interacting, cancer-associated transcription factors in MCF7 cells, a cell line used to model breast cancer. Transcriptomic analysis reveals that L1PA2 transposons also contribute transcription start sites to up-regulated transcripts in MCF7 cells, including some transcripts with established oncogenic properties. In addition, we verified the utility of our pipeline on other transposon subfamilies, as well as on leukemia and lung carcinoma cell lines. We demonstrate that the normally quiescent regulatory activities of transposons can be activated and alter the cancer transcriptome. In particular, the L1PA2 subfamily contributes abundant regulatory sequences, and likely plays a global role in modulating breast cancer transcriptional regulation. Understanding the regulatory impact of L1PA2 on breast cancer genomes provides additional insights into cancer genome regulation, and may provide novel biomarkers for disease diagnosis, prognosis and therapy.Jiayue-Clara JiangJoseph A. RothnagelKyle R. UptonNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-18 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Jiayue-Clara Jiang Joseph A. Rothnagel Kyle R. Upton Integrated transcription factor profiling with transcriptome analysis identifies L1PA2 transposons as global regulatory modulators in a breast cancer model
description	Abstract While transposons are generally silenced in somatic tissues, many transposons escape epigenetic repression in epithelial cancers, become transcriptionally active and contribute to the regulation of human gene expression. We have developed a bioinformatic pipeline for the integrated analysis of transcription factor binding and transcriptomic data to identify transposon-derived promoters that are activated in specific diseases and developmental states. We applied this pipeline to a breast cancer model, and found that the L1PA2 transposon subfamily contributes abundant regulatory sequences to co-ordinated transcriptional regulation in breast cancer. Transcription factor profiling demonstrates that over 27% of L1PA2 transposons harbour co-localised binding sites of functionally interacting, cancer-associated transcription factors in MCF7 cells, a cell line used to model breast cancer. Transcriptomic analysis reveals that L1PA2 transposons also contribute transcription start sites to up-regulated transcripts in MCF7 cells, including some transcripts with established oncogenic properties. In addition, we verified the utility of our pipeline on other transposon subfamilies, as well as on leukemia and lung carcinoma cell lines. We demonstrate that the normally quiescent regulatory activities of transposons can be activated and alter the cancer transcriptome. In particular, the L1PA2 subfamily contributes abundant regulatory sequences, and likely plays a global role in modulating breast cancer transcriptional regulation. Understanding the regulatory impact of L1PA2 on breast cancer genomes provides additional insights into cancer genome regulation, and may provide novel biomarkers for disease diagnosis, prognosis and therapy.
format	article
author	Jiayue-Clara Jiang Joseph A. Rothnagel Kyle R. Upton
author_facet	Jiayue-Clara Jiang Joseph A. Rothnagel Kyle R. Upton
author_sort	Jiayue-Clara Jiang
title	Integrated transcription factor profiling with transcriptome analysis identifies L1PA2 transposons as global regulatory modulators in a breast cancer model
title_short	Integrated transcription factor profiling with transcriptome analysis identifies L1PA2 transposons as global regulatory modulators in a breast cancer model
title_full	Integrated transcription factor profiling with transcriptome analysis identifies L1PA2 transposons as global regulatory modulators in a breast cancer model
title_fullStr	Integrated transcription factor profiling with transcriptome analysis identifies L1PA2 transposons as global regulatory modulators in a breast cancer model
title_full_unstemmed	Integrated transcription factor profiling with transcriptome analysis identifies L1PA2 transposons as global regulatory modulators in a breast cancer model
title_sort	integrated transcription factor profiling with transcriptome analysis identifies l1pa2 transposons as global regulatory modulators in a breast cancer model
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/b7fc12492b4b4d2bb4b821a58664062c
work_keys_str_mv	AT jiayueclarajiang integratedtranscriptionfactorprofilingwithtranscriptomeanalysisidentifiesl1pa2transposonsasglobalregulatorymodulatorsinabreastcancermodel AT josepharothnagel integratedtranscriptionfactorprofilingwithtranscriptomeanalysisidentifiesl1pa2transposonsasglobalregulatorymodulatorsinabreastcancermodel AT kylerupton integratedtranscriptionfactorprofilingwithtranscriptomeanalysisidentifiesl1pa2transposonsasglobalregulatorymodulatorsinabreastcancermodel
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Integrated transcription factor profiling with transcriptome analysis identifies L1PA2 transposons as global regulatory modulators in a breast cancer model

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