The Role of Linker Histones in Carcinogenesis
2021
Linker histones are DNA-binding architectural chromatin proteins involved in the formation of supranucleosomal levels of chromatin packaging. In mammals, 11 variants of these proteins are known, but the functional significance of this diversity is currently not fully defined. In addition to the main structural function, linker histones are involved in regulatory interactions, such as global gene deregulation during carcinogenesis. In turn, these changes in carcinogenesis can affect both linker histones through mutations of their encoding genes or changes in the expression of these genes, and the regulatory systems of the cell, causing a redistribution of linker histone variants in interphase chromatin, disrupting their posttranslational modifications or forming functionally active complexes with them. In some cases, changes in the metabolism of linker histones could be a possible cause of malignant transformation, as well as act as possible prognostic markers. Possible mechanisms of such changes in carcinogenesis are discussed, which also allow us to better understand the functions of linker histone variants and domains of these proteins in normal cells.
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