University of Massachusetts Medical School Faculty Publications
UMMS Affiliation
Department of Molecular, Cellular and Cancer Biology
Publication Date
2018-12-03
Document Type
Article Preprint
Disciplines
Amino Acids, Peptides, and Proteins | Bioinformatics | Cell Biology | Cells | Embryonic Structures | Genetic Phenomena | Genomics | Structural Biology
Abstract
In interphase eukaryotic cells, almost all heterochromatin is located adjacent to the nucleolus or to the nuclear lamina, thus defining Nucleolus Associated Domains (NADs) and Lamina Associated Domains (LADs), respectively. Here, we determined the first genome-scale map of murine NADs in mouse embryonic fibroblasts (MEFs) via deep sequencing of chromatin associated with purified nucleoli. We developed a Bioconductor package called NADfinder and demonstrated that it identifies NADs more accurately than other peak-calling tools, due to its critical feature of chromosome-level local baseline correction. We detected two distinct classes of NADs. Type I NADs associate frequently with both the nucleolar periphery and with the nuclear lamina, and generally display characteristics of constitutive heterochromatin, including late DNA replication, enrichment of H3K9me3 and little gene expression. In contrast, Type II NADs associate with nucleoli but do not overlap with LADs. Type II NADs tend to replicate earlier, display greater gene expression, and are more often enriched in H3K27me3 than Type I NADs. The nucleolar associations of both classes of NADs were confirmed via DNA-FISH, which also detected Type I but not Type II probes enriched at the nuclear lamina. Interestingly, Type II NADs are enriched in distinct gene classes, notably factors important for differentiation and development. In keeping with this, we observed that a Type II NAD is developmentally regulated, present in MEFs but not in undifferentiated embryonic stem (ES) cells.
Keywords
nucleolus associated domains, NADs, chromatin territories, nucleolus, histone modification, genomics, fibroblast, heterochromatin
Rights and Permissions
The copyright holder for this preprint (which was not peer-reviewed) is the author/funder. It is made available under a CC-BY-NC-ND 4.0 International license.
DOI of Published Version
10.1101/484568
Source
bioRxiv 484568; doi: https://doi.org/10.1101/484568. Link to preprint on bioRxiv service.
Journal/Book/Conference Title
bioRxiv
Repository Citation
Vertii A, Ou J, Yu J, Yan A, Pagès H, Liu H, Zhu LJ, Kaufman PD. (2018). Two Contrasting Classes of Nucleolus-Associated Domains in Mouse Fibroblast Heterochromatin. University of Massachusetts Medical School Faculty Publications. https://doi.org/10.1101/484568. Retrieved from https://escholarship.umassmed.edu/faculty_pubs/1608
Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.
Included in
Amino Acids, Peptides, and Proteins Commons, Bioinformatics Commons, Cell Biology Commons, Cells Commons, Embryonic Structures Commons, Genetic Phenomena Commons, Genomics Commons, Structural Biology Commons