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

• Published in: Cell reports (Cambridge) 2016-11, Vol.17 (8), p.2125-2136
• Main Authors: Le Gros, Mark A., Clowney, E. Josephine, Magklara, Angeliki, Yen, Angela, Markenscoff-Papadimitriou, Eirene, Colquitt, Bradley, Myllys, Markko, Kellis, Manolis, Lomvardas, Stavros, Larabell, Carolyn A.
• Format: Article
• Language: English
• Subjects: 60 APPLIED LIFE SCIENCES; Animals; BASIC BIOLOGICAL SCIENCES; Cell Differentiation; Cell Nucleolus - metabolism; chromatin; Chromatin - metabolism; Chromosomal Proteins, Non-Histone - metabolism; differentiation; Epithelial Cells - metabolism; Heterochromatin - metabolism; Imaging, Three-Dimensional; INSTRUMENTATION RELATED TO NUCLEAR SCIENCE AND TECHNOLOGY; Mice, Knockout; Neurogenesis; Neurons - cytology; Neurons - metabolism; nuclear organization; nucleus; Olfactory Bulb - cytology; olfactory sensory neurons; soft X-ray tomography; Tomography, X-Ray
• ISSN: 2211-1247; 2211-1247
• DOI: 10.1016/j.celrep.2016.10.060

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. [Display omitted] •Soft X-ray tomography reveals chromatin networks in olfactory neurons•Chromatin compaction increases during olfactory neurogenesis•Condensed chromatin moves to nuclear core during differentiation•HP1β regulates reorganization of chromatin in mature neurons As part of the IHEC consortium, Le Gros et al. characterize nuclear organization in mouse olfactory neurons throughout differentiation. Quantitative 3D x-ray reconstructions reveal distinct chromatin compartments that form an interconnected network that spans the nucleus and persists during nuclear reorganization. Explore the Cell Press IHEC webportal at www.cell.com/consortium/IHEC.