Determinants of nucleosome organization in primary human cells

By Anton Valouev, Steven M. Johnson, S. Boyd, Cheryl L. Smith, A. Fire, Arend Sidow. 2011

673 citations recorded by the source corpus.

Nucleosomes are the basic packaging units of chromatin, modulating accessibility of regulatory proteins to DNA and thus influencing eukaryotic gene regulation. Elaborate chromatin remodelling mechanisms have evolved that govern nucleosome organization at promoters, regulatory elements, and other functional regions in the genome. Analyses of chromatin landscape have uncovered a variety of mechanisms, including DNA sequence preferences, that can influence nucleosome positions. To identify major determinants of nucleosome organization in the human genome, we used deep sequencing to map nucleosome positions in three primary human cell types and in vitro. A majority of the genome showed substantial flexibility of nucleosome positions, whereas a small fraction showed reproducibly positioned nucleosomes. Certain sites that position in vitro can anchor the formation of nucleosomal arrays that have cell type-specific spacing in vivo. Our results unveil an interplay of sequence-based nucleosome preferences and non-nucleosomal factors in determining nucleosome organization within mammalian cells.

Subfields: Molecular Biology

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Citations in the corpus

Latent enhancers activated by stimulation in differentiated cells. (2013, neutral): “The second possibility is that either nucleosome turnover or spontaneous lateral movements of nucleosomes that are not constrained because of the lack of either adjacent barriers or positioning signals (Valouev et al., 2011) would create windows of opportunity for TF binding, thus eventually leading”
ATAC-seq: A Method for Assaying Chromatin Accessibility Genome-Wide (2015, background): “…this epigenetic structure, providing information on transcription factor binding, the positions of modified and canonical nucleosomes, and chromatin accessibility at regulatory elements such as promoters, enhancers, and insulators (Valouev et al., 2011; Consortium, 2012; Thurman et al., 2012).”
An Integrated Encyclopedia of DNA Elements in the Human Genome (2012, background): “Thus, we confirm on a genome-wide scale that TFs can form barriers around which nucleosomes and histone modifications are arranged in a variety of configurations 63–66 .”
Cell-free DNA comprises an in vivo nucleosome footprint that informs its tissues-of-origin (2016, neutral): “As expected, the WPS correlates with the locations of nucleosomes within strongly positioned arrays, as mapped by other groups with in vitro methods (Gaffney et al., 2012; Valouev et al., 2012) or ancient DNA (Pedersen et al., 2014) (Figure 2B).”
Sequence features and chromatin structure around the genomic regions bound by 119 human transcription factors (2012, methodology): “Furthermore, it was reported that TF binding sites are flanked by multiple well-positioned nucleosomes (Fu et al. 2008; Valouev et al. 2011).”
Pioneer transcription factors: establishing competence for gene expression. (2011, background): “However, reconstitution of genomes into nucleosome arrays in vitro indicates that nucleosome positioning and destabilization are only partially due to intrinsic DNA sequence (Zhang et al. 2009; Valouev et al. 2011).”