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CTCF-dependent chromatin boundaries formed by asymmetric nucleosome arrays with decreased linker length

Clarkson, Christopher T and Deeks, Emma A and Samarista, Ralph and Mamayusupova, Hulkar and Zhurkin, Victor B and Teif, Vladimir B (2019) 'CTCF-dependent chromatin boundaries formed by asymmetric nucleosome arrays with decreased linker length.' Nucleic Acids Research, 47 (21). pp. 11181-11196. ISSN 0305-1048

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The CCCTC-binding factor (CTCF) organises the genome in 3D through DNA loops and in 1D by setting boundaries isolating different chromatin states, but these processes are not well understood. Here we investigate chromatin boundaries in mouse embryonic stem cells, defined by the regions with decreased Nucleosome Repeat Length (NRL) for ~20 nucleosomes near CTCF sites, affecting up to 10% of the genome. We found that the nucleosome-depleted region (NDR) near CTCF is asymmetrically located >40 nucleotides 5’-upstream from the centre of CTCF motif. The strength of CTCF binding to DNA and the presence of cohesin is correlated with the decrease of NRL near CTCF, and anti-correlated with the level of asymmetry of the nucleosome array. Individual chromatin remodellers have different contributions, with Snf2h having the strongest effect on the NRL decrease near CTCF and Chd4 playing a major role in the symmetry breaking. Upon differentiation, a subset of preserved, common CTCF sites maintains asymmetric nucleosome pattern and small NRL. The sites which lost CTCF upon differentiation are characterised by nucleosome rearrangement 3’-downstream, with unchanged NDR 5’-upstream of CTCF motifs. Boundaries of topologically associated chromatin domains frequently contain several inward-oriented CTCF motifs whose effects, described above, add up synergistically.

Item Type: Article
Uncontrolled Keywords: nucleosome; chromatin; CTCF; gene regulation
Divisions: Faculty of Science and Health
Faculty of Science and Health > Life Sciences, School of
SWORD Depositor: Elements
Depositing User: Elements
Date Deposited: 23 Oct 2019 14:28
Last Modified: 06 Jan 2022 14:06

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