The localization of centromere protein A is conserved among tissues.
Abstract: Centromeres are epigenetically specified by the histone H3 variant CENP-A. Although mammalian centromeres are typically associated with satellite DNA, we previously demonstrated that the centromere of horse chromosome 11 (ECA11) is completely devoid of satellite DNA. We also showed that the localization of its CENP-A binding domain is not fixed but slides within an about 500 kb region in different individuals, giving rise to positional alleles. These epialleles are inherited as Mendelian traits but their position can move in one generation. It is still unknown whether centromere sliding occurs during meiosis or during development. Here, we first improve the sequence of the ECA11 centromeric region in the EquCab3.0 assembly. Then, to test whether centromere sliding may occur during development, we map the CENP-A binding domains of ECA11 using ChIP-seq in five tissues of different embryonic origin from the four horses of the equine FAANG (Functional Annotation of ANimal Genomes) consortium. Our results demonstrate that the centromere is localized in the same region in all tissues, suggesting that the position of the centromeric domain is maintained during development.
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Publication Date: 2023-09-21 PubMed ID: 37735603PubMed Central: PMC10514049DOI: 10.1038/s42003-023-05335-7Google Scholar: Lookup
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- Journal Article
- Research Support
- U.S. Gov't
- Non-P.H.S.
- Research Support
- Non-U.S. Gov't
Summary
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Objective Overview
- This study investigates whether the location of the centromere, marked by the protein CENP-A on horse chromosome 11, changes during development by analyzing multiple tissues from the same individuals.
- The results reveal that the position of CENP-A binding remains consistent across different tissues, indicating stable centromere localization throughout development.
Introduction to Centromeres and CENP-A
- Centromeres are essential chromosome regions that ensure accurate segregation during cell division.
- The identity of centromeres is epigenetically specified by a histone H3 variant called CENP-A rather than solely by DNA sequence.
- In most mammals, centromeres associate with repetitive satellite DNA; however, horse chromosome 11 (ECA11) uniquely lacks satellite DNA at its centromere.
Previous Findings Regarding ECA11 Centromere
- The authors previously discovered that the centromere on ECA11 can “slide” or shift its position within a 500 kb region between different individual horses.
- These variable centromere positions are called positional epialleles, inherited like Mendelian genetic traits but capable of moving within a single generation.
- A key unknown was whether this sliding occurs during the formation of reproductive cells (meiosis) or at some point during organismal development after fertilization.
Aims of the Current Study
- Improve the sequence assembly of the ECA11 centromeric region to provide a more accurate reference (updating EquCab3.0).
- Determine if the centromere position changes during development by comparing CENP-A binding sites across different tissues derived from various embryonic origins.
- Use samples from four horses as part of the equine FAANG consortium to analyze these questions with a high level of rigor and standardization.
Methods
- Chromatin immunoprecipitation followed by sequencing (ChIP-seq) was performed to map CENP-A binding domains in five distinct tissues from each horse.
- The tissues selected represented different embryonic germ layers to capture potential developmental differences.
- The improved centromeric region sequence provided a reliable framework for interpreting the ChIP-seq data precisely.
Results
- The position of the CENP-A binding domain on ECA11 was consistent across all five tissues within individual horses.
- No evidence was found for centromere sliding occurring during the developmental stages that generate the sampled tissues.
- Therefore, once established, the positional epiallele of the centromere appears stably maintained throughout the life of the organism in various tissue types.
Conclusions and Implications
- The study supports the idea that centromere sliding is not a continuous developmental process but likely occurs during meiosis or early germline formation.
- These findings contribute to understanding epigenetic inheritance mechanisms controlling centromere location and stability.
- By clarifying when centromere repositioning happens, the research enhances knowledge relevant to chromosome biology, evolution, and genome stability in mammals.
Cite This Article
APA
Cappelletti E, Piras FM, Sola L, Santagostino M, Petersen JL, Bellone RR, Finno CJ, Peng S, Kalbfleisch TS, Bailey E, Nergadze SG, Giulotto E.
(2023).
The localization of centromere protein A is conserved among tissues.
Commun Biol, 6(1), 963.
https://doi.org/10.1038/s42003-023-05335-7 Publication
Researcher Affiliations
- Department of Biology and Biotechnology, University of Pavia, Pavia, Italy.
- Department of Biology and Biotechnology, University of Pavia, Pavia, Italy.
- Department of Biology and Biotechnology, University of Pavia, Pavia, Italy.
- Department of Biology and Biotechnology, University of Pavia, Pavia, Italy.
- Department of Animal Science, University of Nebraska-Lincoln, Lincoln, NE, USA.
- Department of Population Health and Reproduction, School of Veterinary Medicine, University of California-Davis, Davis, CA, USA.
- Veterinary Genetics Laboratory, School of Veterinary Medicine, University of California-Davis, Davis, CA, USA.
- Department of Population Health and Reproduction, School of Veterinary Medicine, University of California-Davis, Davis, CA, USA.
- Department of Population Health and Reproduction, School of Veterinary Medicine, University of California-Davis, Davis, CA, USA.
- Gluck Equine Research Center, University of Kentucky, Lexington, KY, USA.
- Gluck Equine Research Center, University of Kentucky, Lexington, KY, USA.
- Department of Biology and Biotechnology, University of Pavia, Pavia, Italy.
- Department of Biology and Biotechnology, University of Pavia, Pavia, Italy. elena.giulotto@unipv.it.
MeSH Terms
- Humans
- Animals
- Horses
- Centromere Protein A / genetics
- DNA, Satellite
- Centromere / genetics
- Histones
- Meiosis
- Mammals
Conflict of Interest Statement
The authors declare no competing interests.
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