Nucleolus and centromere Tyramide Signal Amplification-Seq reveals variable localization of heterochromatin in different cell types

Genome differential positioning within interphase nuclei remains poorly explored. We extended and validated Tyramide Signal Amplification (TSA)-seq to map genomic regions near nucleoli and pericentric heterochromatin in four human cell lines. Our study confirmed that smaller chromosomes localize closer to nucleoli but further deconvolved this by revealing a preference for chromosome arms below 36-46 Mbp in length. We identified two lamina associated domain subsets through their differential nuclear lamina versus nucleolar positioning in different cell lines which showed distinctive patterns of DNA replication timing and gene expression across all cell lines. Unexpectedly, active, nuclear speckle-associated genomic regions were found near typically repressive nuclear compartments, which is attributable to the close proximity of nuclear speckles and nucleoli in some cell types, and association of centromeres with nuclear speckles in human embryonic stem cells (hESCs). Our study points to a more complex and variable nuclear genome organization than suggested by current models, as revealed by our TSA-seq methodology.

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Publication Details

Journal
Communications Biology
Published
2024-09-13
DOI
https://doi.org/10.1038/s42003-024-06838-7
Citations
18
Primary Topic
Genomics and Chromatin Dynamics
Type
article
Field-Weighted Citation Impact
4.21

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article

Nucleolus and centromere Tyramide Signal Amplification-Seq reveals variable localization of heterochromatin in different cell types

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18 citations
Communications Biology
Genomics and Chromatin Dynamics
4.21
article

Nucleolus and centromere Tyramide Signal Amplification-Seq reveals variable localization of heterochromatin in different cell types

Paul D. Kaufman, David M. Gilbert, Daan Peric‐Hupkes, Pradeep Kumar, Omid Gholamalamdari, Tom van Schaik, Takayo Sasaki, Bas van Steensel, Anastassiia Vertii, Andrew S. Belmont, Yang Zhang, Jian Ma, Liguo Zhang
article en
18 citations

Abstract

Genome differential positioning within interphase nuclei remains poorly explored. We extended and validated Tyramide Signal Amplification (TSA)-seq to map genomic regions near nucleoli and pericentric heterochromatin in four human cell lines. Our study confirmed that smaller chromosomes localize closer to nucleoli but further deconvolved this by revealing a preference for chromosome arms below 36-46 Mbp in length. We identified two lamina associated domain subsets through their differential nuclear lamina versus nucleolar positioning in different cell lines which showed distinctive patterns of DNA replication timing and gene expression across all cell lines. Unexpectedly, active, nuclear speckle-associated genomic regions were found near typically repressive nuclear compartments, which is attributable to the close proximity of nuclear speckles and nucleoli in some cell types, and association of centromeres with nuclear speckles in human embryonic stem cells (hESCs). Our study points to a more complex and variable nuclear genome organization than suggested by current models, as revealed by our TSA-seq methodology.

Communications BiologyVol. 7(1)
University of Illinois Urbana-Champaign (US), University of Massachusetts Chan Medical School (US), The Netherlands Cancer Institute (NL), Oncode Institute (NL), San Diego Biomedical Research Institute (US), Carnegie Mellon University (US)
National Human Genome Research Institute, National Cancer Institute, National Institute of Diabetes and Digestive and Kidney Diseases
Zero hunger
Openalex Percentile: Top 5%
Genomics and Chromatin Dynamics
4.21
DOIOpen Access PDFOpenAlex
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