title: Soft X-Ray Tomography Reveals Gradual Chromatin Compaction and Reorganization during Neurogenesis In Vivo.
abstract: The realization that nuclear distribution of DNA, RNA, and proteins differs between cell types and developmental stages suggests that nuclear organization serves regulatory functions. Understanding the logic of nuclear architecture and how it contributes to differentiation and cell fate commitment remains challenging. Here, we use soft X-ray tomography (SXT) to image chromatin organization, distribution, and biophysical properties during neurogenesis in vivo. Our analyses reveal that chromatin with similar biophysical properties forms an elaborate connected network throughout the entire nucleus. Although this interconnectivity is present in every developmental stage, differentiation proceeds with concomitant increase in chromatin compaction and re-distribution of condensed chromatin toward the nuclear core. HP1β, but not nucleosome spacing or phasing, regulates chromatin rearrangements because it governs both the compaction of chromatin and its interactions with the nuclear envelope. Our experiments introduce SXT as a powerful imaging technology for nuclear architecture.
authors.affiliation: Department of Anatomy, University of California San Francisco, San Francisco, CA 94158, USA; Physical Biosciences Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA; National Center for X-Ray Tomography, University of California San Francisco, San Francisco, CA 94158, USA; Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Le Gros
authors.affiliation: Program in Biomedical Sciences, University of California San Francisco, San Francisco, CA 94158, USA.
authors.forename: E Josephine
authors.initials: EJ
authors.lastname: Clowney
authors.affiliation: Division of Biomedical Research, Institute of Molecular Biology and Biotechnology, Foundation for Research and Technology-Hellas, Ioannina, Greece.
authors.forename: Angeliki
authors.initials: A
authors.lastname: Magklara
authors.affiliation: Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Computer Science and Artificial Intelligence Laboratory, MIT, Cambridge, MA 02139, USA.
authors.forename: Angela
authors.initials: A
authors.lastname: Yen
authors.affiliation: Program in Neurosciences, University of California San Francisco, San Francisco, CA 94158, USA.
authors.forename: Eirene
authors.initials: E
authors.lastname: Markenscoff-Papadimitriou
authors.affiliation: Program in Neurosciences, University of California San Francisco, San Francisco, CA 94158, USA.
authors.forename: Bradley
authors.initials: B
authors.lastname: Colquitt
authors.affiliation: Department of Physics, University of Jyväskylä, Jyväskylä 40014, Finland.
authors.forename: Markko
authors.initials: M
authors.lastname: Myllys
authors.affiliation: Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Computer Science and Artificial Intelligence Laboratory, MIT, Cambridge, MA 02139, USA.
authors.forename: Manolis
authors.initials: M
authors.lastname: Kellis
authors.affiliation: Department of Anatomy, University of California San Francisco, San Francisco, CA 94158, USA; Program in Biomedical Sciences, University of California San Francisco, San Francisco, CA 94158, USA; Program in Neurosciences, University of California San Francisco, San Francisco, CA 94158, USA.
authors.forename: Stavros
authors.initials: S
authors.lastname: Lomvardas
authors.affiliation: Department of Anatomy, University of California San Francisco, San Francisco, CA 94158, USA; Physical Biosciences Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA; National Center for X-Ray Tomography, University of California San Francisco, San Francisco, CA 94158, USA. Electronic address: carolyn.larabell@ucsf.edu.
authors.forename: Carolyn A
authors.initials: CA
authors.lastname: Larabell
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D002466:Cell Nucleolus / Q000378:metabolism; D002843:Chromatin / Q000378:metabolism*; D000090266:Chromobox Protein Homolog 5; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism; D004847:Epithelial Cells / Q000378:metabolism; D006570:Heterochromatin / Q000378:metabolism; D021621:Imaging, Three-Dimensional; D018345:Mice, Knockout; D055495:Neurogenesis; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D009830:Olfactory Bulb / Q000166:cytology; D014056:Tomography, X-Ray
chemical_list: D002843:Chromatin; D002868:Chromosomal Proteins, Non-Histone; D006570:Heterochromatin; D000090266:Chromobox Protein Homolog 5
keywords: chromatin; differentiation; neurogenesis; nuclear organization; nucleus; olfactory sensory neurons; soft X-ray tomography