Upwardly mobile proteins

High Mobility Group proteins (HMGs) are a set of chromatin proteins first identified in the 1970s because they are very abundant and run fast on SDS–PAGE. In these and other properties they resemble histones. And like histones, which have seen a resurgence of interest thanks to the discovery that their modification modulates transcription, HMGs are staging a comeback. They now appear to be important and versatile players in the same complex plot: they regulate the expression of genes in normal or pathological conditions.About a hundred researchers from four continents gathered for 2 days (May 1 and 2, 2000) at the Lister Hill Center of the NIH, Bethesda, to discuss HMGs. Here we report on both the general picture and some of the most novel results (at least to us). Only work published in the last year is cited in the References; for background information, excellent starting points are the reviews by Bustin (1999) and Wegner (1999).### A rose is a rose is a rose (but there are 2 × 3 HMGs)HMGs were discovered by the British scientist H.M. Goodwin, which has led some to speculate that their name reflects the initials of the discoverer, or of Her Majesty's Government. Today, the name refers to two classes of proteins: the canonical HMGs, and HMG‐motif proteins. Canonical HMGs are ubiquitous to eukaryotes but are absent in eubacteria and archaea. They can be divided into three groups that are completely dissimilar from one another at the level of sequence and structure, but are internally homogeneous: the HMG1/2, HMG‐14/17, and HMG‐I/Y families (Table 1). Each family is characterized by a functional sequence motif: the HMG box, the nucleosome binding domain, or the AT‐hook (Figure 1). HMG‐motif proteins contain one of these functional motifs, but the rest of the sequence is different.Figure 1. Structure of AT‐hooks and HMG boxes, as determined by the laboratory of M. Clore (Bethesda, …