Dual-specificity tyrosine-phosphorylation regulated kinase 1A Gene Transcription is regulated by Myocyte Enhancer Factor 2D

Abstract Dual-specificity tyrosine–phosphorylation regulated kinase 1A (DYRK1A) is localized in the Down syndrome critical region of chromosome 21. As a candidate gene responsible for learning defects associated with Down syndrome and Alzheimer’s disease (AD), DYRK1A has been implied to play pivotal...

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Autores principales:	Pin Wang, Luanluan Wang, Long Chen, Xiulian Sun
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/7bd1b2fc44284b2498bea5ed2c46f938
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spelling	oai:doaj.org-article:7bd1b2fc44284b2498bea5ed2c46f9382021-12-02T11:52:41ZDual-specificity tyrosine-phosphorylation regulated kinase 1A Gene Transcription is regulated by Myocyte Enhancer Factor 2D10.1038/s41598-017-07655-12045-2322https://doaj.org/article/7bd1b2fc44284b2498bea5ed2c46f9382017-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-07655-1https://doaj.org/toc/2045-2322Abstract Dual-specificity tyrosine–phosphorylation regulated kinase 1A (DYRK1A) is localized in the Down syndrome critical region of chromosome 21. As a candidate gene responsible for learning defects associated with Down syndrome and Alzheimer’s disease (AD), DYRK1A has been implied to play pivotal roles in cell proliferation and brain development. MEF2D, a member of the myocyte-specific enhancer factor 2 (MEF2) family of transcription factors, was proved to be in control of neuronal cell differentiation and development. Here we demonstrated that MEF2D could upregulate DYRK1A gene expression through specific activation of DYRK1A isoform 5 gene transcription. A MEF2D responsive element from −268 to −254 bp on promoter region of DYRK1A isoform 5 was identified and confirmed by luciferase assay, electrophoretic mobility shift assay (EMSA) and chromatin immunoprecipitation (ChIP). The coordinated expression of DYRK1A and MEF2D in mouse brain development indicated a possibility of the cross-interaction of these two genes during neurodevelopment. The DYRK1A kinase activity was also affected by MEF2D’s transcriptional regulation of DYRK1A. Therefore, the molecular regulation of DYRK1A by MEF2D further supported their involvement in neurodevelopment.Pin WangLuanluan WangLong ChenXiulian SunNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-11 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Pin Wang Luanluan Wang Long Chen Xiulian Sun Dual-specificity tyrosine-phosphorylation regulated kinase 1A Gene Transcription is regulated by Myocyte Enhancer Factor 2D
description	Abstract Dual-specificity tyrosine–phosphorylation regulated kinase 1A (DYRK1A) is localized in the Down syndrome critical region of chromosome 21. As a candidate gene responsible for learning defects associated with Down syndrome and Alzheimer’s disease (AD), DYRK1A has been implied to play pivotal roles in cell proliferation and brain development. MEF2D, a member of the myocyte-specific enhancer factor 2 (MEF2) family of transcription factors, was proved to be in control of neuronal cell differentiation and development. Here we demonstrated that MEF2D could upregulate DYRK1A gene expression through specific activation of DYRK1A isoform 5 gene transcription. A MEF2D responsive element from −268 to −254 bp on promoter region of DYRK1A isoform 5 was identified and confirmed by luciferase assay, electrophoretic mobility shift assay (EMSA) and chromatin immunoprecipitation (ChIP). The coordinated expression of DYRK1A and MEF2D in mouse brain development indicated a possibility of the cross-interaction of these two genes during neurodevelopment. The DYRK1A kinase activity was also affected by MEF2D’s transcriptional regulation of DYRK1A. Therefore, the molecular regulation of DYRK1A by MEF2D further supported their involvement in neurodevelopment.
format	article
author	Pin Wang Luanluan Wang Long Chen Xiulian Sun
author_facet	Pin Wang Luanluan Wang Long Chen Xiulian Sun
author_sort	Pin Wang
title	Dual-specificity tyrosine-phosphorylation regulated kinase 1A Gene Transcription is regulated by Myocyte Enhancer Factor 2D
title_short	Dual-specificity tyrosine-phosphorylation regulated kinase 1A Gene Transcription is regulated by Myocyte Enhancer Factor 2D
title_full	Dual-specificity tyrosine-phosphorylation regulated kinase 1A Gene Transcription is regulated by Myocyte Enhancer Factor 2D
title_fullStr	Dual-specificity tyrosine-phosphorylation regulated kinase 1A Gene Transcription is regulated by Myocyte Enhancer Factor 2D
title_full_unstemmed	Dual-specificity tyrosine-phosphorylation regulated kinase 1A Gene Transcription is regulated by Myocyte Enhancer Factor 2D
title_sort	dual-specificity tyrosine-phosphorylation regulated kinase 1a gene transcription is regulated by myocyte enhancer factor 2d
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/7bd1b2fc44284b2498bea5ed2c46f938
work_keys_str_mv	AT pinwang dualspecificitytyrosinephosphorylationregulatedkinase1agenetranscriptionisregulatedbymyocyteenhancerfactor2d AT luanluanwang dualspecificitytyrosinephosphorylationregulatedkinase1agenetranscriptionisregulatedbymyocyteenhancerfactor2d AT longchen dualspecificitytyrosinephosphorylationregulatedkinase1agenetranscriptionisregulatedbymyocyteenhancerfactor2d AT xiuliansun dualspecificitytyrosinephosphorylationregulatedkinase1agenetranscriptionisregulatedbymyocyteenhancerfactor2d
_version_	1718394993103601664

Dual-specificity tyrosine-phosphorylation regulated kinase 1A Gene Transcription is regulated by Myocyte Enhancer Factor 2D

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