Characterization of a proximal Sp1 response element in the mouse Dlk2 gene promoter

<p>Abstract</p> <p>Background</p> <p>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 <it>Dlk2 </it>is coordinated with that of <it>Dlk1 </it>in several tissues and cell lines. Unlike <it>Dlk1</it>, the mouse <it>Dlk2 </it>gene and its locus at chromosome 17 are not fully characterized.</p> <p>Results</p> <p>The goal of this work was the characterization of <it>Dlk2 </it>mRNA, as well as the analysis of the mechanisms that control its basal transcription. First, we analyzed the <it>Dlk2 </it>transcripts expressed by several mouse cells lines and tissues, and mapped the transcription start site by 5' Rapid Amplification of cDNA Ends. <it>In silico </it>analysis revealed that <it>Dlk2 </it>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 <it>Dlk2 </it>promoter, activates its transcription, and regulates its level of expression.</p> <p>Conclusions</p> <p>Our results provide the first characterization of <it>Dlk2 </it>transcripts, map the location of the <it>Dlk2 </it>core promoter, and show the role of Sp1 as a key regulator of <it>Dlk2 </it>transcription, providing new insights into the molecular mechanisms that contribute to the expression of the <it>Dlk2 </it>gene.</p

The Bell Beaker multiple burial pit of La Atalayuela (La Rioja, Spain): stable isotope insights into diet, identity and mortuary practices in Chalcolithic Iberia.

La Atalayuela is a Middle Chalcolithic (ca. 2900–2500 cal BC) multiple burial pit located in the mid-upper Ebro Valley (north-central Iberia) where a large number of individuals (more than 70) were inhumed. The site shows an apparently constrained period of funerary use, which includes the probable simultaneous burial of a large proportion of the deceased. This offers an outstanding opportunity to investigate the lifeways and identity of the members of what was presumably a single community living and interring their dead at the very beginnings of the Bell Beaker culture in the region. Here, we present stable carbon and nitrogen isotope values on bone collagen from 46 humans. While the overall results are consistent with diets focused on C3 plants and terrestrial animal resources, as would be expected, the variability still demonstrates some interesting patterning. Thus, there is a significant differentiation in δ13C values between burial context base (the earliest funerary use identified, interpreted as a ‘house of the dead’) and the following context a2 (interpreted as a mass grave), supporting the existence of potentially distinct funerary uses. Remains from the vestibule (a structure to the south of the pit interpreted as entrance), whose carbon isotope values also differ from those of a2, have been tentatively associated with base and interpreted as a result of potential bone arrangements prior to the mass interment. Statistically significant age- and sex-related isotopic differences are also identified, which allow social insights, such as possible differential access by children and women to certain food sources, which may in turn reflect a possible sexual division of labour. The results are set in the context of other Late Prehistoric Iberian funerary and isotopic data