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Architectural regulations and Hmg1

Nature Genetics volume 22, pages 215–217 (1999)Cite this article

Without solid foundations, things tend to fall apart. This architectural principle holds true at the molecular level in addition to the more tangible world that we see around us. The foundation stones for the assembly of regulatory nucleoprotein complexes are the histones and the high mobility group (HMG) proteins. HMG proteins are abundant chromosome constituents, originally defined by their chemical properties and mobility on gels—hence the term 'high mobility group'. On page 276 of this issue, Marco Bianchi and colleagues establish the surprising fact that the most studied HMG protein, HMG1, is not essential for packaging DNA into chromosomes in the mouse. Nor is it essential for embryonic and fetal development. Instead, it is required for specific gene regulatory processes that occur only after birth1. This definitive study impacts on the many proposed functions of HMG1 in chromosomal biology and has general implications for the role of 'non-specific' DNA-binding proteins in gene control.

A few years ago many investigators working on gene control considered the HMGs and histones—if they thought about them at all—as obstructive to their transcription experiments. These 'non-specific' DNA-binding proteins were known to 'wrap' DNA, and appeared to serve only as an impediment to the binding of the sequence-specific 'transcriptional' components. In contrast, those focusing on chromatin structure considered the highly conserved histones and HMG proteins to serve the function of wrapping DNA into a monotonous array of repetitive structures that self-associate to form semi-crystalline inert higher-order structures, resistant to bombardment by X-ray, neutron, electron and photon over long periods of time.

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Figure 1: HMG1 is shown positioned on 15 bp of DNA.
Figure 2: HMG-mediated deformation of DNA mediates the assembly of functional nucleoprotein complexes.

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  1. Laboratory of Molecular Embryology, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, 20892-5431, Maryland, USA

    Alan P Wolffe

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Wolffe, A. Architectural regulations and Hmg1. Nat Genet 22, 215–217 (1999). https://doi.org/10.1038/10267

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