Experiments employing whole organisms

The specific regulatory role of HI documented for the Xenopus 5S RNA gene points to the importance of AT-rich tracts in the genome as potential sites of strong and preferential HI binding. Indeed, it has been shown that histone HI is probably involved in the repression of the murine /1-interferon promoter by binding to its upstream AT-rich region [143]. 

In Xenopus, in addition to the role in 5S RNA gene regulation, somatic HI has been shown to be involved in further stages of differentiation. The restriction of myoD expression, a marker for the loss of the ability by ectodermal cells to differentiate into mesoderm, requires the presence of somatic histone HI [144]. Again, the globular domain alone and not the whole HI molecule is required to confer this effect [142]. 

The spectrum of pleiotropic functions of different HI variants in different taxa has yet to be established. With respect to interactions within chromatin, the elucidation of the role of linker histones in transmitting or enhancing the effects of other non-histone proteins will be of particular interest. Given the dynamic behavior of HI in the nucleus, the possibility of auxiliary extrachromosomal functions performed by the free HI pool should be explored. An example of such a function is the recent finding that free HI is involved in the import of adenovirus DNA into the nucleus [158]. Other potential functions, especially at the period of maximum chromatin condensation, could depend on the gradient of free HI around the chromosomes. 

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