title: Characterization of a proximal Sp1 response element in the mouse Dlk2 gene promoter.
abstract: BACKGROUND
  DLK2 is an EGF-like membrane protein, closely related to DLK1, which is involved in adipogenesis. Both proteins interact with the NOTCH1 receptor and are able to modulate its activation. The expression of the gene Dlk2 is coordinated with that of Dlk1 in several tissues and cell lines. Unlike Dlk1, the mouse Dlk2 gene and its locus at chromosome 17 are not fully characterized.
  
  
  RESULTS
  The goal of this work was the characterization of Dlk2 mRNA, as well as the analysis of the mechanisms that control its basal transcription. First, we analyzed the Dlk2 transcripts expressed by several mouse cells lines and tissues, and mapped the transcription start site by 5' Rapid Amplification of cDNA Ends. In silico analysis revealed that Dlk2 possesses a TATA-less promoter containing minimal promoter elements associated with a CpG island, and sequences for Inr and DPE elements. Besides, it possesses six GC-boxes, considered as consensus sites for the transcription factor Sp1. Indeed, we report that Sp1 directly binds to the Dlk2 promoter, activates its transcription, and regulates its level of expression.
  
  
  CONCLUSIONS
  Our results provide the first characterization of Dlk2 transcripts, map the location of the Dlk2 core promoter, and show the role of Sp1 as a key regulator of Dlk2 transcription, providing new insights into the molecular mechanisms that contribute to the expression of the Dlk2 gene.
authors.affiliation: Facultad de Medicina/Centro Regional de Investigaciones Biomédicas, Universidad de Castilla-La Mancha, Calle Almansa 14, 02006 Albacete, Spain.
authors.forename: Samuel
authors.initials: S
authors.lastname: Rivero
authors.forename: Almudena
authors.initials: A
authors.lastname: Ruiz-García
authors.forename: María J M
authors.initials: MJ
authors.lastname: Díaz-Guerra
authors.forename: Jorge
authors.initials: J
authors.lastname: Laborda
authors.forename: José J
authors.initials: JJ
authors.lastname: García-Ramírez
mesh_terms: D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D002460:Cell Line; D018899:CpG Islands; D005786:Gene Expression Regulation; D023061:Gene Order; D020868:Gene Silencing; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics*; D051379:Mice; D057507:Mice, 129 Strain; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D059372:Nucleotide Motifs; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000737:chemistry; D034741:RNA, Small Interfering; D020218:Response Elements; D016329:Sp1 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D024363:Transcription Initiation Site; D014158:Transcription, Genetic; D015533:Transcriptional Activation
chemical_list: C559657:Dlk2 protein, mouse; D036341:Intercellular Signaling Peptides and Proteins; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D016329:Sp1 Transcription Factor