Concluding Remarks

From our current albeit limited knowledge, the incorporation of histone variants into chromatin appears to have major impact on the organization of chromatin in cells. Most importantly, the turnover and the patterns of their posttranslational modifications are highly dynamic and undergo dramatic changes in developing as well as maturing and senescing cells. Thus, histone variant metabolism is likely to be one of the main determinants in chromatin architecture and eventually the regulation and maintenance of developmental gene expression programs. We only are beginning to understand how the manifestation and the progression of cancer and hereditary diseases depend on epigenetic aspects of chromatin regulation by histone variants. Deciphering the functions of histone variants, their modifications, and their interplay within chromatin will be an endeavor for many research laboratories in the upcoming years. The generation of epigenetic maps of the human genome is already on its way.

Along this line, a great challenge of equal importance will be the characterization of multiprotein machineries that are involved in histone variant exchange and thereby regulate the dynamic changes of epigenetic patterning within cells. The identification of these factors will unravel the molecular nature of cancers, infertility, mental disorders, ageing, and degenerative diseases and eventually will help develop new and effective diagnostics and therapeutics.

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