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Differentially accessible, single copy sequences form contiguous domains along metaphase chromosomes that are conserved among multiple tissues

BACKGROUND: During mitosis, chromatin engages in a dynamic cycle of condensation and decondensation. Condensation into distinct units to ensure high fidelity segregation is followed by rapid and reproducible decondensation to produce functional daughter cells. Factors contributing to the reproducibi...

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Autores principales: Hill, Seana L., Rogan, Peter K., Wang, Yi Xuan, Knoll, Joan H. M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8527651/
https://www.ncbi.nlm.nih.gov/pubmed/34670606
http://dx.doi.org/10.1186/s13039-021-00567-w
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author Hill, Seana L.
Rogan, Peter K.
Wang, Yi Xuan
Knoll, Joan H. M.
author_facet Hill, Seana L.
Rogan, Peter K.
Wang, Yi Xuan
Knoll, Joan H. M.
author_sort Hill, Seana L.
collection PubMed
description BACKGROUND: During mitosis, chromatin engages in a dynamic cycle of condensation and decondensation. Condensation into distinct units to ensure high fidelity segregation is followed by rapid and reproducible decondensation to produce functional daughter cells. Factors contributing to the reproducibility of chromatin structure between cell generations are not well understood. We investigated local metaphase chromosome condensation along mitotic chromosomes within genomic intervals showing differential accessibility (DA) between homologs. DA was originally identified using short sequence-defined single copy (sc) DNA probes of < 5 kb in length by fluorescence in situ hybridization (scFISH) in peripheral lymphocytes. These structural differences between metaphase homologs are non-random, stable, and heritable epigenetic marks which have led to the proposed function of DA as a marker of chromatin memory. Here, we characterize the organization of DA intervals into chromosomal domains by identifying multiple DA loci in close proximity to each other and examine the conservation of DA between tissues. RESULTS: We evaluated multiple adjacent scFISH probes at 6 different DA loci from chromosomal regions 2p23, 3p24, 12p12, 15q22, 15q24 and 20q13 within peripheral blood T-lymphocytes. DA was organized within domains that extend beyond the defined boundaries of individual scFISH probes. Based on hybridizations of 2 to 4 scFISH probes per domain, domains ranged in length from 16.0 kb to 129.6 kb. Transcriptionally inert chromosomal DA regions in T-lymphocytes also demonstrated conservation of DA in bone marrow and fibroblast cells. CONCLUSIONS: We identified novel chromosomal regions with allelic differences in metaphase chromosome accessibility and demonstrated that these accessibility differences appear to be aggregated into contiguous domains extending beyond individual scFISH probes. These domains are encompassed by previously established topologically associated domain (TAD) boundaries. DA appears to be a conserved feature of human metaphase chromosomes across different stages of lymphocyte differentiation and germ cell origin, consistent with its proposed role in maintenance of intergenerational cellular chromosome memory. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13039-021-00567-w.
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spelling pubmed-85276512021-10-25 Differentially accessible, single copy sequences form contiguous domains along metaphase chromosomes that are conserved among multiple tissues Hill, Seana L. Rogan, Peter K. Wang, Yi Xuan Knoll, Joan H. M. Mol Cytogenet Research BACKGROUND: During mitosis, chromatin engages in a dynamic cycle of condensation and decondensation. Condensation into distinct units to ensure high fidelity segregation is followed by rapid and reproducible decondensation to produce functional daughter cells. Factors contributing to the reproducibility of chromatin structure between cell generations are not well understood. We investigated local metaphase chromosome condensation along mitotic chromosomes within genomic intervals showing differential accessibility (DA) between homologs. DA was originally identified using short sequence-defined single copy (sc) DNA probes of < 5 kb in length by fluorescence in situ hybridization (scFISH) in peripheral lymphocytes. These structural differences between metaphase homologs are non-random, stable, and heritable epigenetic marks which have led to the proposed function of DA as a marker of chromatin memory. Here, we characterize the organization of DA intervals into chromosomal domains by identifying multiple DA loci in close proximity to each other and examine the conservation of DA between tissues. RESULTS: We evaluated multiple adjacent scFISH probes at 6 different DA loci from chromosomal regions 2p23, 3p24, 12p12, 15q22, 15q24 and 20q13 within peripheral blood T-lymphocytes. DA was organized within domains that extend beyond the defined boundaries of individual scFISH probes. Based on hybridizations of 2 to 4 scFISH probes per domain, domains ranged in length from 16.0 kb to 129.6 kb. Transcriptionally inert chromosomal DA regions in T-lymphocytes also demonstrated conservation of DA in bone marrow and fibroblast cells. CONCLUSIONS: We identified novel chromosomal regions with allelic differences in metaphase chromosome accessibility and demonstrated that these accessibility differences appear to be aggregated into contiguous domains extending beyond individual scFISH probes. These domains are encompassed by previously established topologically associated domain (TAD) boundaries. DA appears to be a conserved feature of human metaphase chromosomes across different stages of lymphocyte differentiation and germ cell origin, consistent with its proposed role in maintenance of intergenerational cellular chromosome memory. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13039-021-00567-w. BioMed Central 2021-10-20 /pmc/articles/PMC8527651/ /pubmed/34670606 http://dx.doi.org/10.1186/s13039-021-00567-w Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Hill, Seana L.
Rogan, Peter K.
Wang, Yi Xuan
Knoll, Joan H. M.
Differentially accessible, single copy sequences form contiguous domains along metaphase chromosomes that are conserved among multiple tissues
title Differentially accessible, single copy sequences form contiguous domains along metaphase chromosomes that are conserved among multiple tissues
title_full Differentially accessible, single copy sequences form contiguous domains along metaphase chromosomes that are conserved among multiple tissues
title_fullStr Differentially accessible, single copy sequences form contiguous domains along metaphase chromosomes that are conserved among multiple tissues
title_full_unstemmed Differentially accessible, single copy sequences form contiguous domains along metaphase chromosomes that are conserved among multiple tissues
title_short Differentially accessible, single copy sequences form contiguous domains along metaphase chromosomes that are conserved among multiple tissues
title_sort differentially accessible, single copy sequences form contiguous domains along metaphase chromosomes that are conserved among multiple tissues
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8527651/
https://www.ncbi.nlm.nih.gov/pubmed/34670606
http://dx.doi.org/10.1186/s13039-021-00567-w
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