HMGA proteins are chromatin “architectural modifiers”, bearing conserved “AT-hook” motifs with which they bind to DNA AT-rich regions to assist in gene transcription. In mammals, including humans, two HMGAs, HMGA1 and HMGA2, have been described, encoded by separate genes. These genes are actively transcribed in proliferating and undifferentiated tissues during embryogenesis, but not in adult differentiated tissues; however, they are re-activated in tumor progression. In Xenopus, the hmga1 gene is apparently missing, while we have cloned Xenopus hmga2 (Xhmga2) and studied its developmental expression. By whole mount in situ hybridisation (WISH), localized transcripts are first detected at neurula stages, in the presumptive central nervous system (CNS) and eye field, and in the neural crest cell (NCC) presumptive territory. At tailbud and tadpole stages, Xhmga2 mRNA is detected in the CNS, in the otic vesicles, in migrating neural crest cells and their derivatives, in the notochord and in the medio-lateral mesoderm. We are currently focusing our attention on the possible role of Xhmga2 in NCCs. Morpholino-injected embryos typically show very strong abnormalities in the branchial region, where the branchial arches are lost or severely disrupted. Analysis of NCC molecular markers show severe downregulation or absence of Xtwist, and Xdll4 expression at the tailbud stage. TUNEL staining on injected embryos shows that extensive cell death occurs in the regions normally occupied by NCC. Injection of control morpholinos did not lead to similar alterations. These data suggest that Xhmga2 is required for NCC survival, possibly during the stage when NCC migrate in the visceral arches. We have also identified two divergent members of the HMGA family in the Xenopus genome, that we have named XHMGAx and XHMGAx2. The deduced proteins are characterized by an unusual number of AT hooks (8 or 6 respectively). We have cloned the XHMGAx cDNA and we are currently studying its expression pattern during development. Finally, we are performing detailed biochemical analysis of the HMGA2 and XHMGAx proteins to look for conserved and divergent aspects between the human and Xenopus proteins in terms of DNA binding properties and of protein-protein interactions.

HMGA2 and HMGAx proteins in Xenopus laevis

VIGNALI, ROBERT;
2010

Abstract

HMGA proteins are chromatin “architectural modifiers”, bearing conserved “AT-hook” motifs with which they bind to DNA AT-rich regions to assist in gene transcription. In mammals, including humans, two HMGAs, HMGA1 and HMGA2, have been described, encoded by separate genes. These genes are actively transcribed in proliferating and undifferentiated tissues during embryogenesis, but not in adult differentiated tissues; however, they are re-activated in tumor progression. In Xenopus, the hmga1 gene is apparently missing, while we have cloned Xenopus hmga2 (Xhmga2) and studied its developmental expression. By whole mount in situ hybridisation (WISH), localized transcripts are first detected at neurula stages, in the presumptive central nervous system (CNS) and eye field, and in the neural crest cell (NCC) presumptive territory. At tailbud and tadpole stages, Xhmga2 mRNA is detected in the CNS, in the otic vesicles, in migrating neural crest cells and their derivatives, in the notochord and in the medio-lateral mesoderm. We are currently focusing our attention on the possible role of Xhmga2 in NCCs. Morpholino-injected embryos typically show very strong abnormalities in the branchial region, where the branchial arches are lost or severely disrupted. Analysis of NCC molecular markers show severe downregulation or absence of Xtwist, and Xdll4 expression at the tailbud stage. TUNEL staining on injected embryos shows that extensive cell death occurs in the regions normally occupied by NCC. Injection of control morpholinos did not lead to similar alterations. These data suggest that Xhmga2 is required for NCC survival, possibly during the stage when NCC migrate in the visceral arches. We have also identified two divergent members of the HMGA family in the Xenopus genome, that we have named XHMGAx and XHMGAx2. The deduced proteins are characterized by an unusual number of AT hooks (8 or 6 respectively). We have cloned the XHMGAx cDNA and we are currently studying its expression pattern during development. Finally, we are performing detailed biochemical analysis of the HMGA2 and XHMGAx proteins to look for conserved and divergent aspects between the human and Xenopus proteins in terms of DNA binding properties and of protein-protein interactions.
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11568/142344
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