Induction of dystrophin Dp71 expression during neuronal differentiation: Opposite roles of Sp1 and AP2α in Dp71 promoter activity

Sara Luz Morales-Lázaro, Ricardo González-Ramírez, Pablo Gómez, Victor Tapia-Ramírez, Mario Bermúdez De León, Bulmaro Cisneros

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

In this study, we delineated the molecular mechanisms that modulate Dp71 expression during neuronal differentiation, using the N1E-115 cell line. We demonstrated that Dp71 expression is up-regulated in response to cAMP-mediated neuronal differentiation of these cells, and that this induction is controlled at promoter level. Functional deletion analysis of the Dp71 promoter revealed that a 5′-flanking 159-bp DNA fragment that contains Sp1 and AP2α binding sites is necessary and sufficient for basal expression of this TATA-less promoter, as well as for its induction during neuronal differentiation. Electrophoretic mobility shift and chromatin immunoprecipitation assays revealed that Sp1 and AP2α bind to their respective DNA elements within the Dp71 basal promoter. Overall, mutagenesis assays on the Sp1 and AP2α binding sites, over-expression of Sp1 and AP2α, as well as knock-down experiments on Sp1 and AP2α gene expression established that Dp71 basal expression is controlled by the combined action of Sp1 and AP2α, which act as activator and repressor, respectively. Furthermore, we demonstrated that induction of Dp71 expression in differentiated cells is the result of the maintenance of positive regulation exerted by Sp1, as well as of the loss of AP2α binding, which ultimately releases the promoter from repression. © 2009 International Society for Neurochemistry.
Original languageEnglish
Pages (from-to)474-485
Number of pages12
JournalJournal of Neurochemistry
DOIs
Publication statusPublished - 1 Jan 2010
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Cellular and Molecular Neuroscience

Fingerprint Dive into the research topics of 'Induction of dystrophin Dp71 expression during neuronal differentiation: Opposite roles of Sp1 and AP2α in Dp71 promoter activity'. Together they form a unique fingerprint.

  • Cite this