High impact information on Sox5

• Embryos, in which Sox9 was deleted after mesenchymal condensations, exhibited a severe generalized chondrodysplasia, similar to that in Sox5; Sox6 double-null mutant mice [1].
• Expression of Sox5 and Sox6, two other Sox genes involved in chondrogenesis, was no longer detected [1].
• Sox5 and Sox6 permit formation of growth plate columnar zones by keeping chondroblasts proliferating and by delaying chondrocyte prehypertrophy [2].
• Anti-Sox-5 antibody was used to analyse expression of Sox-5 in pre-pubertal testis and in fractionated spermatogenic cells [3].
• Sox-5 is restricted to post-meiotic germ cells, being found at highest levels in round spermatids [3].

Biological context of Sox5

• In common with Sox5, Sox6 is highly expressed in the adult mouse testis and the HMG domains of both proteins bind to the sequence 5'-AACAAT-3'. This suggests that the two genes may have overlapping functions in the regulation of gene expression during spermatogenesis in the adult mouse [4].
• SOX5 cDNAs isolated from a human adult testis cDNA library show a high similarity with the mouse Sox5 transcript over a large region identical in all the human cDNAs [5].
• L-Sox5 and Sox6 are thus redundant, potent enhancers of chondroblast functions, thereby essential for endochondral skeleton formation [6].
• Sox-5 is a DNA binding protein and binding site selection assays suggest that it can bind specifically to oligonucleotides containing the consensus motif AACAAT [3].
• Sox-5 is one of a family of genes which show homology to the HMG box region of the testis determining gene SRY [7].

Anatomical context of Sox5

• Sox13 and L-Sox5 showed expression in most of the pancreatic epithelial cells between embryonic days 12.5 and 14 [8].
• Sox5 and Sox6 promote the development of a highly proliferating pool of chondroblasts between the epiphyses and metaphyses of future long bones [2].
• In conclusion, Sox5 and Sox6 are needed for the establishment of multilayered growth plates, and thereby for proper and timely development of endochondral bones [2].
• Our analysis of Sox5/Sox6 double mutants, in which the chondroprogenitors are unable to differentiate into cartilage, reveals that the two cell fates arising from the sclerotome, axial tendon and cartilage are alternative lineages, and that cartilage differentiation is required to actively repress tendon development in the dorsolateral sclerotome [9].
• Sox5 and Sox6 which are expressed in post-meiotic germ cells bound TSBR4 [10].

Associations of Sox5 with chemical compounds

• This identified (i) an additional 91 amino acids upstream of the previously designated methionine start codon in the original cDNA, and (ii) an intron encoded within the HMG box/DNA binding domain in exactly the same position as that found in the Sox5, -13 and -17 genes [11].

Other interactions of Sox5

• DNA binding and bending properties of the post-meiotically expressed Sry-related protein Sox-5 [7].
• In contrast, overexpression of another Sox member, Sox5, triggered no such trans-activation of mor DP-driven luciferase activity or DNA-protein binding activity [12].
• The HMG domain is encoded by exons XI and XII, separated by an intron that is conserved among Sox-5, Sox-13, and Sox-17 [13].
• These results suggest that reduced expression of Osterix in combination with Sox9-Sox5 expression is important for the onset of condylar (secondary) cartilage formation [14].
• The mouse Sox5 gene encodes a protein containing the leucine zipper and the Q box [15].

Analytical, diagnostic and therapeutic context of Sox5

• Circular dichroism spectroscopy of the Sox-5 HMG box and its specific complex with DNA shows an alteration in the DNA spectrum, perhaps as a consequence of DNA bending, but none in the protein spectrum on complex formation [7].
• In vitro footprinting and gel retardation assays demonstrate that Sox-5 binds specifically to the sequence AACAAT with moderately high affinity (Kd of approximately 10(-9) M) [7].
• We have used indirect immunofluorescence to show that Sox-5 protein is localized to the nucleus of post-meiotic round spermatids in the mouse testis [7].
• The thermal properties and energetics of formation of 10, 12 and 16 bp DNA duplexes, specifically interacting with the HMG box of Sox-5, have been studied by isothermal titration calorimetry (ITC) and differential scanning calorimetry (DSC) [16].
• The energetics of the Sox-5 HMG box interaction with DNA duplexes, containing the recognition sequence AACAAT, were studied by fluorescence spectroscopy, isothermal titration calorimetry (ITC) and differential scanning calorimetry (DSC) [17].

References