Elevated EGR1 binding at enhancers in excitatory neurons correlates with neuronal subtype-specific epigenetic regulation

dc.contributor.authorYin, Liduoen
dc.contributor.authorXu, Xiguangen
dc.contributor.authorConacher, Benjaminen
dc.contributor.authorLin, Yuen
dc.contributor.authorCarrillo, Gabriela L.en
dc.contributor.authorCun, Yupengen
dc.contributor.authorFox, Michael A.en
dc.contributor.authorLu, Xuemeien
dc.contributor.authorXie, Hehuangen
dc.date.accessioned2025-08-18T17:18:13Zen
dc.date.available2025-08-18T17:18:13Zen
dc.date.issued2025-08-11en
dc.date.updated2025-08-17T03:09:12Zen
dc.description.abstractBackground: Brain development and neuronal cell specification are accompanied by epigenetic changes that enable the regulation of diverse gene expression patterns. During these processes, transcription factors interact with cell-type-specific epigenetic marks, binding to unique sets of cis-regulatory elements in different cell types. However, the detailed mechanisms through which cell-type-specific gene regulation is established in neurons remain to be explored. Results: In this study, we conducted a comparative histone modification analysis between excitatory and inhibitory neurons. Our results revealed that neuronal cell-type-specific histone modifications are enriched in super enhancer regions that contain abundant EGR1 motifs. Further CUT&RUN assay confirmed that excitatory neurons exhibit more EGR1 binding sites, primarily located in enhancers. Integrative analysis demonstrated that EGR1 binding is strongly correlated with various epigenetic markers of open chromatin regions and is linked to distinct gene pathways specific to neuronal subtypes. In inhibitory neurons, most genomic regions containing EGR1 binding sites become accessible during early embryonic stages, whereas super enhancers in excitatory neurons, which also host EGR1 binding sites, gain accessibility during postnatal stages. Conclusions: This study highlights the crucial role of transcription factor binding, such as EGR1, to enhancer regions, which may be key to establishing cell-type-specific gene regulation in neurons.en
dc.description.versionPublished versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.citationBMC Biology. 2025 Aug 11;23(1):251en
dc.identifier.doihttps://doi.org/10.1186/s12915-025-02357-xen
dc.identifier.urihttps://hdl.handle.net/10919/137525en
dc.language.isoenen
dc.rightsCreative Commons Attribution-NonCommercial-NoDerivatives 4.0 Internationalen
dc.rights.holderThe Author(s)en
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/en
dc.titleElevated EGR1 binding at enhancers in excitatory neurons correlates with neuronal subtype-specific epigenetic regulationen
dc.title.serialBMC Biologyen
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten

Files

Original bundle
Now showing 1 - 1 of 1
Loading...
Thumbnail Image
Name:
12915_2025_Article_2357.pdf
Size:
6.8 MB
Format:
Adobe Portable Document Format
Description:
Published version
License bundle
Now showing 1 - 1 of 1
Name:
license.txt
Size:
1.5 KB
Format:
Item-specific license agreed upon to submission
Description: