Network of Dynamic Interactions between Histone H1 and High-Mobility-Group Proteins in Chromatin

Abstract

Histone H1 and the high-mobility group (HMG) proteins are chromatin binding proteins that regulate gene expression by modulating the compactness of the chromatin fiber and affecting the ability of regulatory factors to access their nucleosomal targets. Histone H1 stabilizes the higher-order chromatin structure and decreases nucleosomal access, while the HMG proteins decrease the compactness of the chromatin fiber and enhance the accessibility of chromatin targets to regulatory factors. Here we show that in living cells, each of the three families of HMG proteins weakens the binding of H1 to nucleosomes by dynamically competing for chromatin binding sites. The HMG families weaken H1 binding synergistically and do not compete among each other, suggesting that they affect distinct H1 binding sites. We suggest that a network of dynamic and competitive interactions involving HMG proteins and H1, and perhaps other structural proteins, constantly modulates nucleosome accessibility and the local structure of the chromatin fiber.The chromatin fiber is a dynamic, malleable structure that is targeted by numerous regulatory factors that modify the histones and the DNA and remodel the structure of the nucleosome. The dynamics of the chromatin fiber reflect the combined action of numerous chromatin modifiers, including architectural proteins such as histone H1 and members of the high-mobility group (HMG) protein superfamily. The interaction of histone H1 with nucleosomes stabilizes the higherorder, compact chromatin structure (57, 61), thereby restricting the ability of regulatory factors, nucleosome remodeling complexes, and histone modifiers to access their chromatin binding sites (17,27,28,30,32,34). Loss of H1 results in both up regulation and down regulation of specific gene expression (2,26,53,56), suggesting that the protein affects the action of both positive and negative transcriptional regulators. Experiments with H1 knockout mice demonstrate the existence of cellular mechanisms that strive to maintain a constant level of H1 and that reduction of H1 beyond a critical point is not compatible with normal embryonic development (21). Thus, factors that modulate the interaction of H1 with nucleosomes may affect a variety of chromatin-related processes and participate in genetic regulatory mechanisms.The HMG superfamily is composed of three families: HMGB, HMGA, and HMGN, each family being characterized by a distinct DNA or chromatin binding motif (12). These non-histones decompact the higher-order chromatin structure and promote the binding of nuclear regulatory factors (1,12,49,58). Footprinting analysis and in vitro binding assays (29,64) showed that the chromatin binding sites of the HMG proteins are similar to those of H1 and suggested that HMG proteins and H1 compete for the same binding sites, and recent photobleaching experiments demonstrated that HMGN proteins affect the binding of H1 to chromatin in living cells (16). Photobleaching techniques like fluorescence recovery after photobleaching (FRAP), which is used...

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Remodeling of chromatin structure in senescent cells and its potential impact on tumor suppression and aging

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N- and C-terminal Domains Determine Differential Nucleosomal Binding Geometry and Affinity of Linker Histone Isotypes H10 and H1c

“…Linker histones are a family of lysine-rich proteins that bind at or near the point at which DNA enters and exits the nucleosomal core and organize an additional ϳ20 bp of linker DNA, to form the chromatosome (6 -8). Although binding of linker histones further stabilizes chromatin into higher order structures (9 -12), these proteins interact with chromatin in a dynamic manner as components of a highly intricate and active network of chromatinbinding proteins (13)(14)(15)(16).…”