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

Abstract

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.