2022
DOI: 10.1101/2022.09.15.507958
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BRG1 generates subnucleosomes that expand OCT4 binding and function beyond DNA motifs at enhancers

Abstract: Mammalian SWI/SNF complexes (mSWI/SNF) are ATP-dependent chromatin remodelling factors that possess tumour suppressor properties1. Brg1 (Smarca4), the catalytic subunit of mSWI/SNF, is essential for chromatin opening at enhancers2,3, but the detailed mechanism of this activity remains unclear. Using mouse embryonic stem (ES) cells, we show that Brg1 generates subnucleosomal particles which protect genomic DNA fragments of 50-80 bp in length from micrococcal nuclease (MNase) digestion. These particles, which co… Show more

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Cited by 1 publication
(2 citation statements)
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“…In budding yeast, fragile nucleosomes are generated by the action of chromatin remodellers of the SWI/SNF family (Brahma and Henikoff, 2019). In mESCs, BRG1 has recently been suggested to act on fragile nucleosomes at enhancers to generate MNase-sensitive sub-nucleosomal hemisome particles that facilitate OCT4 binding (preprint; Nocente et al, 2022). Given the impact of H3K115 acetylation on nucleosome stability in vitro (Manohar et al, 2009;Simon et al, 2011), it is plausible that H3K115 acetylation facilitates the action of BRG1 in further destabilisation of fragile nucleosomes at enhancers.…”
Section: Discussionmentioning
confidence: 99%
See 1 more Smart Citation
“…In budding yeast, fragile nucleosomes are generated by the action of chromatin remodellers of the SWI/SNF family (Brahma and Henikoff, 2019). In mESCs, BRG1 has recently been suggested to act on fragile nucleosomes at enhancers to generate MNase-sensitive sub-nucleosomal hemisome particles that facilitate OCT4 binding (preprint; Nocente et al, 2022). Given the impact of H3K115 acetylation on nucleosome stability in vitro (Manohar et al, 2009;Simon et al, 2011), it is plausible that H3K115 acetylation facilitates the action of BRG1 in further destabilisation of fragile nucleosomes at enhancers.…”
Section: Discussionmentioning
confidence: 99%
“…CTCF binding is known to create arrays of well positioned nucleosomes on both sides of its binding site (Fu et al, 2008;Owens et al, 2019). Though CTCF binding was originally thought to exclude nucleosomes, fragile nucleosomes and very small sub-nucleosomal fragments have been detected at CTCF binding sites (Voong et al, 2016;Klein et al, 2023) (preprint;Nocente et al, 2022). To examine the distribution of H3K115ac and its relationship to sub-nucleosomes at and around CTCF sites, we called CTCF motifs and intersected them with published CTCF ChIP-seq peaks in mESC (Mas et al, 2018).…”
Section: H3k115ac Marks Fragile Nucleosomes At and Around Ctcf Bindin...mentioning
confidence: 99%