ABSTRACT
The Sox gene family consists of several genes related by encoding a 79 amino acid DNA-binding domain known as the HMG box. This box shares strong sequence similarity to that of the testis determining protein SRY. SOX proteins are transcription factors having critical roles in the regulation of diverse developmental processes in the animal kingdom. We have characterised the human SOX7 gene and compared it to its mouse orthologue. Chromosomal mapping analyses localised mouse Sox7 on band D of mouse chromosome 14, and assigned human SOX7 in a region of shared synteny on human chromosome 8 (8p22). A detailed expression analysis was performed in both species. Sox7 mRNA was detected during embryonic development in many tissues, most abundantly in brain, heart, lung, kidney, prostate, colon and spleen, suggesting a role in their respective differentiation and development. In addition, mouse Sox7 expression was shown to parallel mouse Sox18 mRNA localisation in diverse situations. Our studies also demonstrate the presence of a functional transactivation domain in SOX7 protein C-terminus, as well as the ability of SOX7 protein to significantly reduce Wnt/beta-catenin-stimulated transcription. In view of these and other findings, we suggest different modes of action for SOX7 inside the cell including repression of Wnt signalling.
Subject(s)
DNA-Binding Proteins/genetics , DNA-Binding Proteins/metabolism , Gene Expression Profiling , High Mobility Group Proteins/genetics , High Mobility Group Proteins/metabolism , Physical Chromosome Mapping , Proto-Oncogene Proteins/antagonists & inhibitors , Proto-Oncogene Proteins/physiology , Trans-Activators , Transcription Factors/metabolism , Transcriptional Activation , Zebrafish Proteins , Amino Acid Sequence , Animals , Cell Line , Chromosomes, Human, Pair 8/genetics , Cloning, Molecular , Cytoskeletal Proteins/antagonists & inhibitors , Cytoskeletal Proteins/metabolism , DNA-Binding Proteins/antagonists & inhibitors , DNA-Binding Proteins/chemistry , Expressed Sequence Tags , Gene Expression Regulation, Developmental , High Mobility Group Proteins/chemistry , Humans , Lymphoid Enhancer-Binding Factor 1 , Mice , Molecular Sequence Data , Open Reading Frames/genetics , Protein Structure, Tertiary , RNA, Messenger/genetics , RNA, Messenger/metabolism , SOXF Transcription Factors , Sequence Alignment , Signal Transduction , Synteny , Transcription Factors/antagonists & inhibitors , Transcription Factors/chemistry , Transcription Factors/genetics , Wnt Proteins , beta CateninABSTRACT
Traditional staining methods, plus indirect immunoperoxidase techniques for IgE and mast cell tryptase (MCTr) were used to study the mast cells (MCs) of multiple sclerosis (MS) and normal brains. The MCs varied in number in MS amongst perivascular inflammatory cells as well as free in the parenchyma, especially inside and around "chronic active' plaques. Since MCs do not migrate, and rarely divide in maturity, they must have developed locally. Staining for IgE was moderately strong on and within MCs, and weak within some plasma cells. MCTr reacted strongly both within CNS and outside it. Being a strong neutral proteinase. MCTr, plus IgE, could conceivably have played some role in the pathogenesis of the MS plaques.