Genome-wide chromatin accessibility analyses provide a map for enhancing optic nerve regeneration

Abstract Retinal Ganglion Cells (RGCs) lose their ability to grow axons during development. Adult RGCs thus fail to regenerate their axons after injury, leading to vision loss. To uncover mechanisms that promote regeneration of RGC axons, we identified transcription factors (TF) and open chromatin r...

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Autores principales:	Wolfgang Pita-Thomas, Tassia Mangetti Gonçalves, Ajeet Kumar, Guoyan Zhao, Valeria Cavalli
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/3c37702a6f1543b5968d79e033cbdc1b
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spelling	oai:doaj.org-article:3c37702a6f1543b5968d79e033cbdc1b2021-12-02T16:26:22ZGenome-wide chromatin accessibility analyses provide a map for enhancing optic nerve regeneration10.1038/s41598-021-94341-y2045-2322https://doaj.org/article/3c37702a6f1543b5968d79e033cbdc1b2021-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-94341-yhttps://doaj.org/toc/2045-2322Abstract Retinal Ganglion Cells (RGCs) lose their ability to grow axons during development. Adult RGCs thus fail to regenerate their axons after injury, leading to vision loss. To uncover mechanisms that promote regeneration of RGC axons, we identified transcription factors (TF) and open chromatin regions that are enriched in rat embryonic RGCs (high axon growth capacity) compared to postnatal RGCs (low axon growth capacity). We found that developmental stage-specific gene expression changes correlated with changes in promoter chromatin accessibility. Binding motifs for TFs such as CREB, CTCF, JUN and YY1 were enriched in the regions of the chromatin that were more accessible in embryonic RGCs. Proteomic analysis of purified rat RGC nuclei confirmed the expression of TFs with potential role in axon growth such as CREB, CTCF, YY1, and JUND. The CREB/ATF binding motif was widespread at the open chromatin region of known pro-regenerative TFs, supporting a role of CREB in regulating axon regeneration. Consistently, overexpression of CREB fused to the VP64 transactivation domain in mouse RGCs promoted axon regeneration after optic nerve injury. Our study provides a map of the chromatin accessibility during RGC development and highlights that TF associated with developmental axon growth can stimulate axon regeneration in mature RGC.Wolfgang Pita-ThomasTassia Mangetti GonçalvesAjeet KumarGuoyan ZhaoValeria CavalliNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-17 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Wolfgang Pita-Thomas Tassia Mangetti Gonçalves Ajeet Kumar Guoyan Zhao Valeria Cavalli Genome-wide chromatin accessibility analyses provide a map for enhancing optic nerve regeneration
description	Abstract Retinal Ganglion Cells (RGCs) lose their ability to grow axons during development. Adult RGCs thus fail to regenerate their axons after injury, leading to vision loss. To uncover mechanisms that promote regeneration of RGC axons, we identified transcription factors (TF) and open chromatin regions that are enriched in rat embryonic RGCs (high axon growth capacity) compared to postnatal RGCs (low axon growth capacity). We found that developmental stage-specific gene expression changes correlated with changes in promoter chromatin accessibility. Binding motifs for TFs such as CREB, CTCF, JUN and YY1 were enriched in the regions of the chromatin that were more accessible in embryonic RGCs. Proteomic analysis of purified rat RGC nuclei confirmed the expression of TFs with potential role in axon growth such as CREB, CTCF, YY1, and JUND. The CREB/ATF binding motif was widespread at the open chromatin region of known pro-regenerative TFs, supporting a role of CREB in regulating axon regeneration. Consistently, overexpression of CREB fused to the VP64 transactivation domain in mouse RGCs promoted axon regeneration after optic nerve injury. Our study provides a map of the chromatin accessibility during RGC development and highlights that TF associated with developmental axon growth can stimulate axon regeneration in mature RGC.
format	article
author	Wolfgang Pita-Thomas Tassia Mangetti Gonçalves Ajeet Kumar Guoyan Zhao Valeria Cavalli
author_facet	Wolfgang Pita-Thomas Tassia Mangetti Gonçalves Ajeet Kumar Guoyan Zhao Valeria Cavalli
author_sort	Wolfgang Pita-Thomas
title	Genome-wide chromatin accessibility analyses provide a map for enhancing optic nerve regeneration
title_short	Genome-wide chromatin accessibility analyses provide a map for enhancing optic nerve regeneration
title_full	Genome-wide chromatin accessibility analyses provide a map for enhancing optic nerve regeneration
title_fullStr	Genome-wide chromatin accessibility analyses provide a map for enhancing optic nerve regeneration
title_full_unstemmed	Genome-wide chromatin accessibility analyses provide a map for enhancing optic nerve regeneration
title_sort	genome-wide chromatin accessibility analyses provide a map for enhancing optic nerve regeneration
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/3c37702a6f1543b5968d79e033cbdc1b
work_keys_str_mv	AT wolfgangpitathomas genomewidechromatinaccessibilityanalysesprovideamapforenhancingopticnerveregeneration AT tassiamangettigoncalves genomewidechromatinaccessibilityanalysesprovideamapforenhancingopticnerveregeneration AT ajeetkumar genomewidechromatinaccessibilityanalysesprovideamapforenhancingopticnerveregeneration AT guoyanzhao genomewidechromatinaccessibilityanalysesprovideamapforenhancingopticnerveregeneration AT valeriacavalli genomewidechromatinaccessibilityanalysesprovideamapforenhancingopticnerveregeneration
_version_	1718384046642298880

Genome-wide chromatin accessibility analyses provide a map for enhancing optic nerve regeneration

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