Abstract
High mobility group 1 (HMG1) protein is an abundant component of all mammalian nuclei, and related proteins exist in all eukaryotes1,2. HMG1 binds linear DNA with moderate affinity and no sequence specificity3, but bends the double helix significantly on binding through the minor groove4. It binds with high affinity to DNA that is already sharply bent, such as linker DNA at the entry and exit of nucleosomes5,6,7; thus, it is considered a structural protein of chromatin. HMG1 is also recruited to DNA by interactions with proteins required for basal and regulated transcription8,9,10,11,12,13 and V(D)J recombination14,15. Here we generate mice harbouring deleted Hmg1. Hmg1–/– pups are born alive, but die within 24 hours due to hypoglycaemia. Hmg1-deficient mice survive for several days if given glucose parenterally, then waste away with pleiotropic defects (but no alteration in the immune repertoire). Cell lines lacking Hmg1 grow normally, but the activation of gene expression by the glucocorticoid receptor (GR, encoded by the gene Grl1) is impaired. Thus, Hmg1 is not essential for the overall organization of chromatin in the cell nucleus, but is critical for proper transcriptional control by specific transcription factors.
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Acknowledgements
We thank G. Bouvier and F. Watrin for generating ES mutant clones; A. Plück and the EMBL Transgenic Facility for generating Hmg1 +/- mice on a pure 129Sv genetic background; M. Pezzo for mouse blood tests; A. De Luigi and M.G. De Simoni for corticosterone measurements; L. Ronfani for control experiments; T. Ravasi for establishing cell lines; F. Duranti for personal support; and D. Edwards, F. Barbetti, L. Falqui, P. Dellabona, G. Ferrari, F. Tronche and G. Schütz for help with reagents and suggestions. S.C. was a recipient of fellowships from Universita' di Milano and Centro Italiano Biotecnologie. Supported by Associazione Italiana Ricerca sul Cancro, Ministero dell'Universita' e della Ricerca Scientifica and the European Union (grant FMRX-CT97-0109).
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Calogero, S., Grassi, F., Aguzzi, A. et al. The lack of chromosomal protein Hmg1 does not disrupt cell growth but causes lethal hypoglycaemia in newborn mice. Nat Genet 22, 276–280 (1999). https://doi.org/10.1038/10338
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DOI: https://doi.org/10.1038/10338
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