National Academy of Sciences, Proceedings of the National Academy of Sciences, 25(117), p. 14251-14258, 2020
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Significance Eukaryotic genomes harbor a vast number of “selfish” DNA elements, including transposable elements and repetitive sequences. They constitute nearly 50% of the human genome and need to be silenced to maintain the integrity of the genome. Aberrant expression of such sequences, possibly due to failure of silencing mechanisms, is associated with human diseases, including cancer. Silencing of these “selfish” DNAs involves methylation of specific lysine residues in the nucleosome core particles that help package these DNA elements into chromatin in the cell nucleus. Here we demonstrate that H1 linker histones, the most abundant chromatin-binding proteins, are critical for silencing of these sequences, by promoting repressive lysine methylation and further compacting these elements into more condensed chromatin structures.