University of Massachusetts Medical School Faculty Publications

UMMS Affiliation

Department of Molecular, Cellular and Cancer Biology; Graduate School of Biomedical Sciences

Publication Date

2019-08-20

Document Type

Article Preprint

Disciplines

Amino Acids, Peptides, and Proteins | Cell Biology | Cells | Computational Biology | Embryonic Structures | Genomics

Abstract

Background Heterochromatin in eukaryotic interphase cells frequently localizes to the nucleolar periphery (nucleolus-associated domains, NADs) and the nuclear lamina (lamina-associated domains, LADs). Gene expression in somatic cell NADs is generally low, but NADs have not been characterized in mammalian stem cells.

Results Here, we generated the first genome-wide map of NADs in mouse embryonic stem cells (mESCs) via deep sequencing of chromatin associated with biochemically-purified nucleoli. As we had observed in mouse embryonic fibroblasts (MEFs), the large Type I subset of NADs overlaps with constitutive LADs and is enriched for features of constitutive heterochromatin, including late replication timing and low gene density and expression levels. Conversely, the Type II NAD subset overlaps with loci that are not lamina-associated, but in mESCs, Type II NADs are much less abundant than in MEFs. mESC NADs are also much less enriched in H3K27me3 modified regions than are NADs in MEFs. Additionally, comparision of MEF and mESC NADs revealed enrichment of developmentally regulated genes in cell type-specific NADs. Together, these data indicate that NADs are a developmentally dynamic component of heterochromatin.

Conclusions These studies implicate association with the nucleolar periphery as a mechanism for developmentally-regulated gene silencing, and will facilitate future studies of NADs during mESC differentiation.

Keywords

nucleolus associated domains, NADs, embryonic stem cell, mouse, histone modification, Genomics

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The copyright holder for this preprint (which was not peer-reviewed) is the author/funder.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

10.1101/740480

Source

bioRxiv 740480; doi: https://doi.org/10.1101/740480. Link to preprint on bioRxiv service

Journal/Book/Conference Title

bioRxiv

Creative Commons License

Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.

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