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bioRxiv · 10.1101/2023.11.30.569460

Histone N-tails modulate sequence-specific positioning of nucleosomes

Zhurkin, V. B.·Cui, F.·Nikitina, T.·Guiblet, W. M.
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Abstract

The precise mechanisms governing sequence-dependent positioning of nucleosomes on DNA remain unknown in detail. Existing algorithms, taking into account the sequence-dependent deformability of DNA and its interactions with the histone globular domains, predict rotational setting of only 65% of human nucleosomes mapped in vivo. To uncover novel factors responsible for the nucleosome positioning, we analyzed potential involvement of the histone N-tails in this process. To this aim, we reconstituted the H2A/H4 N-tailless nucleosomes on human BRCA1 DNA ([~]100 kb) and compared their positions and sequences with those of the wild-type nucleosomes. In the case of H2A tailless nucleosomes, the AT content of DNA sequences is changed locally at superhelical location (SHL) {+/-}4, while maintaining the same rotational setting as their wild-type counterparts. Conversely, the H4 tailless nucleosomes display widespread changes of the AT content near SHL {+/-}1 and SHL {+/-}2, where the H4 N-tails interact with DNA. Furthermore, a substantial number of H4 tailless nucleosomes exhibit rotational setting opposite to that of the wild-type nucleosomes. Thus, our findings strongly suggest that the histone N-tails are operative in selection of nucleosome positions, which may have wide-ranging implications for epigenetic modulation of chromatin states.

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Zhurkin, V. B., Cui, F., Nikitina, T., Guiblet, W. M.. 2023-11-30. Histone N-tails modulate sequence-specific positioning of nucleosomes. https://doi.org/10.1101/2023.11.30.569460

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