Absence of S100A4 in the mouse lens induces an aberrant retina-specific differentiation program and cataract

Abstract S100A4, a member of the S100 family of multifunctional calcium-binding proteins, participates in several physiological and pathological processes. In this study, we demonstrate that S100A4 expression is robustly induced in differentiating fiber cells of the ocular lens and that S100A4 (−/−)...

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Autores principales:	Rupalatha Maddala, Junyuan Gao, Richard T. Mathias, Tylor R. Lewis, Vadim Y. Arshavsky, Adriana Levine, Jonathan M. Backer, Anne R. Bresnick, Ponugoti V. Rao
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/c5d12a9b1ee845928e568c3467712a88
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spelling	oai:doaj.org-article:c5d12a9b1ee845928e568c3467712a882021-12-02T13:24:37ZAbsence of S100A4 in the mouse lens induces an aberrant retina-specific differentiation program and cataract10.1038/s41598-021-81611-y2045-2322https://doaj.org/article/c5d12a9b1ee845928e568c3467712a882021-01-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-81611-yhttps://doaj.org/toc/2045-2322Abstract S100A4, a member of the S100 family of multifunctional calcium-binding proteins, participates in several physiological and pathological processes. In this study, we demonstrate that S100A4 expression is robustly induced in differentiating fiber cells of the ocular lens and that S100A4 (−/−) knockout mice develop late-onset cortical cataracts. Transcriptome profiling of lenses from S100A4 (−/−) mice revealed a robust increase in the expression of multiple photoreceptor- and Müller glia-specific genes, as well as the olfactory sensory neuron-specific gene, S100A5. This aberrant transcriptional profile is characterized by corresponding increases in the levels of proteins encoded by the aberrantly upregulated genes. Ingenuity pathway network and curated pathway analyses of differentially expressed genes in S100A4 (−/−) lenses identified Crx and Nrl transcription factors as the most significant upstream regulators, and revealed that many of the upregulated genes possess promoters containing a high-density of CpG islands bearing trimethylation marks at histone H3K27 and/or H3K4, respectively. In support of this finding, we further documented that S100A4 (−/−) knockout lenses have altered levels of trimethylated H3K27 and H3K4. Taken together, our findings suggest that S100A4 suppresses the expression of retinal genes during lens differentiation plausibly via a mechanism involving changes in histone methylation.Rupalatha MaddalaJunyuan GaoRichard T. MathiasTylor R. LewisVadim Y. ArshavskyAdriana LevineJonathan M. BackerAnne R. BresnickPonugoti V. RaoNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-16 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Rupalatha Maddala Junyuan Gao Richard T. Mathias Tylor R. Lewis Vadim Y. Arshavsky Adriana Levine Jonathan M. Backer Anne R. Bresnick Ponugoti V. Rao Absence of S100A4 in the mouse lens induces an aberrant retina-specific differentiation program and cataract
description	Abstract S100A4, a member of the S100 family of multifunctional calcium-binding proteins, participates in several physiological and pathological processes. In this study, we demonstrate that S100A4 expression is robustly induced in differentiating fiber cells of the ocular lens and that S100A4 (−/−) knockout mice develop late-onset cortical cataracts. Transcriptome profiling of lenses from S100A4 (−/−) mice revealed a robust increase in the expression of multiple photoreceptor- and Müller glia-specific genes, as well as the olfactory sensory neuron-specific gene, S100A5. This aberrant transcriptional profile is characterized by corresponding increases in the levels of proteins encoded by the aberrantly upregulated genes. Ingenuity pathway network and curated pathway analyses of differentially expressed genes in S100A4 (−/−) lenses identified Crx and Nrl transcription factors as the most significant upstream regulators, and revealed that many of the upregulated genes possess promoters containing a high-density of CpG islands bearing trimethylation marks at histone H3K27 and/or H3K4, respectively. In support of this finding, we further documented that S100A4 (−/−) knockout lenses have altered levels of trimethylated H3K27 and H3K4. Taken together, our findings suggest that S100A4 suppresses the expression of retinal genes during lens differentiation plausibly via a mechanism involving changes in histone methylation.
format	article
author	Rupalatha Maddala Junyuan Gao Richard T. Mathias Tylor R. Lewis Vadim Y. Arshavsky Adriana Levine Jonathan M. Backer Anne R. Bresnick Ponugoti V. Rao
author_facet	Rupalatha Maddala Junyuan Gao Richard T. Mathias Tylor R. Lewis Vadim Y. Arshavsky Adriana Levine Jonathan M. Backer Anne R. Bresnick Ponugoti V. Rao
author_sort	Rupalatha Maddala
title	Absence of S100A4 in the mouse lens induces an aberrant retina-specific differentiation program and cataract
title_short	Absence of S100A4 in the mouse lens induces an aberrant retina-specific differentiation program and cataract
title_full	Absence of S100A4 in the mouse lens induces an aberrant retina-specific differentiation program and cataract
title_fullStr	Absence of S100A4 in the mouse lens induces an aberrant retina-specific differentiation program and cataract
title_full_unstemmed	Absence of S100A4 in the mouse lens induces an aberrant retina-specific differentiation program and cataract
title_sort	absence of s100a4 in the mouse lens induces an aberrant retina-specific differentiation program and cataract
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/c5d12a9b1ee845928e568c3467712a88
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Absence of S100A4 in the mouse lens induces an aberrant retina-specific differentiation program and cataract

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