Varying levels of X chromosome coalescence in female somatic cells alters the balance of X-linked dosage compensation and is implicated in female-dominant systemic lupus erythematosus

Abstract The three-dimensional organization of the genome in mammalian interphase nuclei is intrinsically linked to the regulation of gene expression. Whole chromosome territories and their encoded gene loci occupy preferential positions within the nucleus that changes according to the expression pr...

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Autores principales:	Agnieszka I. Laskowski, Daniel S. Neems, Kyle Laster, Chelsee Strojny-Okyere, Ellen L. Rice, Iwona M. Konieczna, Jessica H. Voss, James M. Mathew, Joseph R. Leventhal, Rosalind Ramsey-Goldman, Erica D. Smith, Steven T. Kosak
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2019
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/f3f068a3414d4bb58406abd7df6067b9
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spelling	oai:doaj.org-article:f3f068a3414d4bb58406abd7df6067b92021-12-02T15:08:59ZVarying levels of X chromosome coalescence in female somatic cells alters the balance of X-linked dosage compensation and is implicated in female-dominant systemic lupus erythematosus10.1038/s41598-019-44229-92045-2322https://doaj.org/article/f3f068a3414d4bb58406abd7df6067b92019-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-019-44229-9https://doaj.org/toc/2045-2322Abstract The three-dimensional organization of the genome in mammalian interphase nuclei is intrinsically linked to the regulation of gene expression. Whole chromosome territories and their encoded gene loci occupy preferential positions within the nucleus that changes according to the expression profile of a given cell lineage or stage. To further illuminate the relationship between chromosome organization, epigenetic environment, and gene expression, here we examine the functional organization of chromosome X and corresponding X-linked genes in a variety of healthy human and disease state X diploid (XX) cells. We observe high frequencies of homologous chromosome X colocalization (or coalescence), typically associated with initiation of X-chromosome inactivation, occurring in XX cells outside of early embryogenesis. Moreover, during chromosome X coalescence significant changes in Xist, H3K27me3, and X-linked gene expression occur, suggesting the potential exchange of gene regulatory information between the active and inactive X chromosomes. We also observe significant differences in chromosome X coalescence in disease-implicated lymphocytes isolated from systemic lupus erythematosus (SLE) patients compared to healthy controls. These results demonstrate that X chromosomes can functionally interact outside of embryogenesis when X inactivation is initiated and suggest a potential gene regulatory mechanism aberration underlying the increased frequency of autoimmunity in XX individuals.Agnieszka I. LaskowskiDaniel S. NeemsKyle LasterChelsee Strojny-OkyereEllen L. RiceIwona M. KoniecznaJessica H. VossJames M. MathewJoseph R. LeventhalRosalind Ramsey-GoldmanErica D. SmithSteven T. KosakNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 9, Iss 1, Pp 1-13 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Agnieszka I. Laskowski Daniel S. Neems Kyle Laster Chelsee Strojny-Okyere Ellen L. Rice Iwona M. Konieczna Jessica H. Voss James M. Mathew Joseph R. Leventhal Rosalind Ramsey-Goldman Erica D. Smith Steven T. Kosak Varying levels of X chromosome coalescence in female somatic cells alters the balance of X-linked dosage compensation and is implicated in female-dominant systemic lupus erythematosus
description	Abstract The three-dimensional organization of the genome in mammalian interphase nuclei is intrinsically linked to the regulation of gene expression. Whole chromosome territories and their encoded gene loci occupy preferential positions within the nucleus that changes according to the expression profile of a given cell lineage or stage. To further illuminate the relationship between chromosome organization, epigenetic environment, and gene expression, here we examine the functional organization of chromosome X and corresponding X-linked genes in a variety of healthy human and disease state X diploid (XX) cells. We observe high frequencies of homologous chromosome X colocalization (or coalescence), typically associated with initiation of X-chromosome inactivation, occurring in XX cells outside of early embryogenesis. Moreover, during chromosome X coalescence significant changes in Xist, H3K27me3, and X-linked gene expression occur, suggesting the potential exchange of gene regulatory information between the active and inactive X chromosomes. We also observe significant differences in chromosome X coalescence in disease-implicated lymphocytes isolated from systemic lupus erythematosus (SLE) patients compared to healthy controls. These results demonstrate that X chromosomes can functionally interact outside of embryogenesis when X inactivation is initiated and suggest a potential gene regulatory mechanism aberration underlying the increased frequency of autoimmunity in XX individuals.
format	article
author	Agnieszka I. Laskowski Daniel S. Neems Kyle Laster Chelsee Strojny-Okyere Ellen L. Rice Iwona M. Konieczna Jessica H. Voss James M. Mathew Joseph R. Leventhal Rosalind Ramsey-Goldman Erica D. Smith Steven T. Kosak
author_facet	Agnieszka I. Laskowski Daniel S. Neems Kyle Laster Chelsee Strojny-Okyere Ellen L. Rice Iwona M. Konieczna Jessica H. Voss James M. Mathew Joseph R. Leventhal Rosalind Ramsey-Goldman Erica D. Smith Steven T. Kosak
author_sort	Agnieszka I. Laskowski
title	Varying levels of X chromosome coalescence in female somatic cells alters the balance of X-linked dosage compensation and is implicated in female-dominant systemic lupus erythematosus
title_short	Varying levels of X chromosome coalescence in female somatic cells alters the balance of X-linked dosage compensation and is implicated in female-dominant systemic lupus erythematosus
title_full	Varying levels of X chromosome coalescence in female somatic cells alters the balance of X-linked dosage compensation and is implicated in female-dominant systemic lupus erythematosus
title_fullStr	Varying levels of X chromosome coalescence in female somatic cells alters the balance of X-linked dosage compensation and is implicated in female-dominant systemic lupus erythematosus
title_full_unstemmed	Varying levels of X chromosome coalescence in female somatic cells alters the balance of X-linked dosage compensation and is implicated in female-dominant systemic lupus erythematosus
title_sort	varying levels of x chromosome coalescence in female somatic cells alters the balance of x-linked dosage compensation and is implicated in female-dominant systemic lupus erythematosus
publisher	Nature Portfolio
publishDate	2019
url	https://doaj.org/article/f3f068a3414d4bb58406abd7df6067b9
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Varying levels of X chromosome coalescence in female somatic cells alters the balance of X-linked dosage compensation and is implicated in female-dominant systemic lupus erythematosus

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