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Cell Rep. 2016 Nov 15;17(8):2125-2136. doi: 10.1016/j.celrep.2016.10.060.

Soft X-Ray Tomography Reveals Gradual Chromatin Compaction and Reorganization during Neurogenesis In Vivo.

Author information

1
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.
2
Program in Biomedical Sciences, University of California San Francisco, San Francisco, CA 94158, USA.
3
Division of Biomedical Research, Institute of Molecular Biology and Biotechnology, Foundation for Research and Technology-Hellas, Ioannina, Greece.
4
Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Computer Science and Artificial Intelligence Laboratory, MIT, Cambridge, MA 02139, USA.
5
Program in Neurosciences, University of California San Francisco, San Francisco, CA 94158, USA.
6
Department of Physics, University of Jyväskylä, Jyväskylä 40014, Finland.
7
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.
8
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.

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.

KEYWORDS:

chromatin; differentiation; neurogenesis; nuclear organization; nucleus; olfactory sensory neurons; soft X-ray tomography

PMID:
27851973
PMCID:
PMC5135017
DOI:
10.1016/j.celrep.2016.10.060
[Indexed for MEDLINE]
Free PMC Article

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