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

Autor:	Guoyan Zhao, Valeria Cavalli, Wolfgang Pita-Thomas, Ajeet Kumar, Tassia Mangetti Gonçalves
Jazyk:	angličtina
Rok vydání:	2021
Předmět:	Retinal Ganglion Cells 0301 basic medicine genetic structures Science Gene Expression Biology CREB Retinal ganglion Article Mice 03 medical and health sciences Transactivation 0302 clinical medicine medicine Animals Epigenetics in the nervous system Axon Regeneration and repair in the nervous system Transcription factor Multidisciplinary Regeneration (biology) Optic Nerve CREB-Binding Protein Axons Chromatin eye diseases Nerve Regeneration Rats Cell biology 030104 developmental biology medicine.anatomical_structure nervous system CTCF Optic Nerve Injuries biology.protein Medicine sense organs 030217 neurology & neurosurgery Transcription Factors
Zdroj:	Scientific Reports, Vol 11, Iss 1, Pp 1-17 (2021) Scientific Reports
ISSN:	2045-2322
Popis:	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.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::8521162ee393813e997107edd40c2f72 https://doaj.org/article/3c37702a6f1543b5968d79e033cbdc1b Zobrazit plný text záznamu Plný text ve formátu PDF Plný text ve formátu HTML
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