Histone HI

Linker histone HI is found at half the molar concentration of the other histones, and it was long believed that every nucleosome also contained a single HI molecule in order to compact chromatin. However, X-ray diffraction experiments required only the four core histones and DNA to reconstitute the diffraction pattern obtained with in vivo chromatin, indicating that HI is not essential (Kornberg and Thomas, 1974). Nevertheless, the HI protein, which consists of N-terminal, C-terminal and central winged-helix domains, aids chromatin compaction in vitro. Recent studies identified sub-domains within the unstructured C-terminal domain, which induce chromatin fiber folding (Lu and Hansen, 2004). HI binds to DNA through its winged-helix domain, but cannot bind to the histone oetamer on its own. Instead, HI binds to the nucleosome close to where the DNA enters and exits.

Linker histones likely play a role in regulation rather than in structure alone, as yeast lacking the homolog of HI survive (Shen et al., 1995). Additionally, HI knockouts in Tetrahymena and mouse 3T3 cells resulted in down-regulation, as well as up-regulation of certain genes (Brown et al., 1997). As with most regulatory proteins, HI is evolutionarily divergent and several isoforms exist. Mammals contain six somatic HI subtypes, which are expressed at various levels in different tissues, cell-cycle phases and developmental stages (Wang et al., 1997). Specifically, histone H1.2 translocates from the nucleus to the mitochondria and signals cytochrome c release in apoptosis and Hlb is recruited by a homeobox transcription factor Msxl to repress transcription of the muscle-specific determinant MyoD (Konishi et al., 2003; Lee et al., 2004). Examples such as these highlight Hi's role as a transcription factor.

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