Abstract
High Mobility Group A proteins (HMGA1 and HMGA2) are architectural nuclear factors involved in development, cell differentiation, and cancer formation and progression. Here we report the cloning, developmental expression and functional analysis of a new multi-AT-hook factor in Xenopus laevis (XHMG-AT-hook) that exists in three different isoforms. Xhmg-at-hook1 and 3 isoforms, but not isoform 2, are expressed throughout the entire development of Xenopus, both in the maternal and zygotic phase. Localized transcripts are present in the animal pole in the early maternal phase; during the zygotic phase, mRNA can be detected in the developing central nervous system (CNS), including the eye, and in the neural crest. We show evidence that XHMG-AT-hook proteins differ from typical HMGA proteins in terms of their properties in DNA binding and in protein/protein interaction. Finally, we provide evidence that they are involved in early CNS development and in neural crest differentiation.
Highlights
High Mobility Group A proteins (HMGA1a, HMGA1b and HMGA2) are chromatin architectural factors involved in embryonic development and neoplastic transformation
Database searches with the deduced protein sequence from our cDNA identified one almost identical sequence in Xenopus laevis and another one shared by both Xenopus laevis and Xenopus tropicalis (NM_001110735 and NM_ 001079207, respectively)
The two other sequences (NM_001110735 and NM 001079207) code for a conserved protein, that we named XHMG-AT-hook3, of 276 aa in Xenopus laevis and 278 aa in Xenopus tropicalis, that is clearly related to XHMG-AT-hook1 and 2 but contains 6 instead of 8 AT-hooks (Fig. 1A)
Summary
High Mobility Group A proteins (HMGA1a, HMGA1b and HMGA2) are chromatin architectural factors involved in embryonic development and neoplastic transformation. HMGA are architectural chromatin modifiers because by binding to DNA they can affect its structure, and by interacting with other nuclear proteins they can participate in the assembling of complexes involved in regulating the expression of several genes that are crucial for cell growth, proliferation, and differentiation [2,3]. HMGA2 haploinsufficiency is associated with growth retardation and reduced height [13,14]. These reports underline an involvement of HMGA in development and in cell commitment
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