title: Chromatin fibers are formed by heterogeneous groups of nucleosomes in vivo.
abstract: Nucleosomes help structure chromosomes by compacting DNA into fibers. To gain insight into how nucleosomes are arranged in vivo, we combined quantitative super-resolution nanoscopy with computer simulations to visualize and count nucleosomes along the chromatin fiber in single nuclei. Nucleosomes assembled in heterogeneous groups of varying sizes, here termed "clutches," and these were interspersed with nucleosome-depleted regions. The median number of nucleosomes inside clutches and their compaction defined as nucleosome density were cell-type-specific. Ground-state pluripotent stem cells had, on average, less dense clutches containing fewer nucleosomes and clutch size strongly correlated with the pluripotency potential of induced pluripotent stem cells. RNA polymerase II preferentially associated with the smallest clutches while linker histone H1 and heterochromatin were enriched in the largest ones. Our results reveal how the chromatin fiber is formed at nanoscale level and link chromatin fiber architecture to stem cell state.
authors.affiliation: Centre for Genomic Regulation (CRG), Dr Aiguader 88, 08003 Barcelona, Spain; Universitat Pompeu Fabra (UPF), Dr Aiguader 88, 08003 Barcelona, Spain.
authors.forename: Maria Aurelia
authors.initials: MA
authors.lastname: Ricci
authors.affiliation: ICFO, Institut de Ciències Fotòniques, Mediterranean Technology Park, 08860 Castelldefels, Barcelona, Spain.
authors.forename: Carlo
authors.initials: C
authors.lastname: Manzo
authors.affiliation: ICFO, Institut de Ciències Fotòniques, Mediterranean Technology Park, 08860 Castelldefels, Barcelona, Spain; Institució Catalana de Recerca i Estudis Avançats (ICREA), 08010 Barcelona, Spain.
authors.forename: María Filomena
authors.initials: MF
authors.lastname: García-Parajo
authors.affiliation: ICFO, Institut de Ciències Fotòniques, Mediterranean Technology Park, 08860 Castelldefels, Barcelona, Spain. Electronic address: melike.lakadamyali@icfo.es.
authors.forename: Melike
authors.initials: M
authors.lastname: Lakadamyali
authors.affiliation: Centre for Genomic Regulation (CRG), Dr Aiguader 88, 08003 Barcelona, Spain; Universitat Pompeu Fabra (UPF), Dr Aiguader 88, 08003 Barcelona, Spain; Institució Catalana de Recerca i Estudis Avançats (ICREA), 08010 Barcelona, Spain. Electronic address: pia.cosma@crg.es.
authors.forename: Maria Pia
authors.initials: MP
authors.lastname: Cosma
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D002843:Chromatin / Q000737:chemistry* / Q000378:metabolism; D003198:Computer Simulation; D053595:Embryonic Stem Cells / Q000737:chemistry / Q000378:metabolism; D055106:Genome-Wide Association Study; D006657:Histones / Q000378:metabolism; D006801:Humans; D007399:Interphase; D051379:Mice; D009154:Mutation; D009707:Nucleosomes / Q000737:chemistry* / Q000378:metabolism / Q000648:ultrastructure*; D039904:Pluripotent Stem Cells / Q000737:chemistry / Q000378:metabolism; D012319:RNA Polymerase II / Q000378:metabolism
chemical_list: D002843:Chromatin; D006657:Histones; D009707:Nucleosomes; D012319:RNA Polymerase II