Transcriptional regulation of CRMP5 controls neurite outgrowth through Sox5

Abstract

Transcriptional regulation of proteins involved in neuronal polarity is a key process that underlies the ability of neurons to transfer information in the central nervous system. The Collapsin Response Mediator Protein (CRMP) family is best known for its role in neurite outgrowth regulation conducting to neuronal polarity and axonal guidance, including CRMP5 that drives dendrite differentiation. Although CRMP5 is able to control dendritic development, the regulation of its expression remains poorly understood. Here we identify a Sox5 consensus binding sequence in the putative promoter sequence upstream of the CRMP5 gene. By luciferase assays we show that Sox5 increases CRMP5 promoter activity, but not if the putative Sox5 binding site is mutated. We demonstrate that Sox5 can physically bind to the CRMP5 promoter DNA in gel mobility shift and chromatin immunoprecipitation assays. Using a combination of real-time RT-PCR and quantitative immunocytochemistry, we provide further evidence for a Sox5-dependent upregulation of CRMP5 transcription and protein expression in N1E115 cells: a commonly used cell line model for neuronal differentiation. Furthermore, we report that increasing Sox5 levels in this neuronal cell line inhibits neurite outgrowth. This inhibition requires CRMP5 because CRMP5 knockdown prevents the Sox5-dependent effect. We confirm the physiological relevance of the Sox5-CRMP5 pathway in the regulation of neurite outgrowth using mouse primary hippocampal neurons. These findings identify Sox5 as a critical modulator of neurite outgrowth through the selective activation of CRMP5 expression.

Long noncoding RNA neuroblastoma-associated transcript 1 gene inhibits malignant cellular phenotypes of bladder cancer through miR-21/SOCS6 axis

“…Some lncRNAs could combine with microRNAs and form complex regulatory networks, and then modulate the expression and function of microRNAs 30 , 31 . In addition, noncoding RNAs ordinarily form ribonucleoprotein (RNP) complexes with their partner proteins to exert their functions and miRNAs assemble with argonaute (Ago) family proteins into the effector complex called RISC that mediates the target gene silencing 32 .…”

Discovering human transcription factor physical interactions with genetic variants, novel DNA motifs, and repetitive elements using enhanced yeast one-hybrid assays

“…This is consistent with the role of GATA4 and GATA5 in heart development and angiogenesis and the role of GATA4 in neuronal development and function (Lawson and Mellon 1998;Holtzinger and Evans 2007;Walsh and Shiojima 2007;Ang et al 2016). Similarly, genes that contain more than one copy of the UW.Motif.0167 in their promoters are associated with dendritic spine development, among other biological processes, as are SOX2, SOX5, and SOX11 (Whitney et al 2014;Hoshiba et al 2016;Naudet et al 2018). Altogether, this shows that our approach can identify TFs that bind to uncharacterized motifs, including zinc fingers, which are generally difficult to study, and that the TFs identified are likely to be functionally related to their potential target genes.…”

Discovering human transcription factor interactions with genetic variants, novel DNA motifs, and repetitive elements using enhanced yeast one-hybrid assays

“…This is consistent with the role of GATA4 and GATA5 in heart development and angiogenesis, and the role of GATA4 in neuronal development and function (Lawson and Mellon 1998;Holtzinger and Evans 2007;Walsh and Shiojima 2007;Ang et al 2016). Similarly, genes that contain more than one copy of the UW.Motif.0167 in their promoters are associated with dendritic spine development, among other biological processes, as are SOX2, SOX5, and SOX11 (Whitney et al 2014;Hoshiba et al 2016;Naudet et al 2018). Altogether, this shows that our approach can identify TFs that bind to uncharacterized motifs, including zinc fingers which are generally difficult to study, and that the TFs identified are functionally related to their potential target genes.…”