Epigenetic control of region‐specific transcriptional programs in mouse cerebellar and cortical astrocytes

Astrocytes from the cerebral cortex (CTX) and cerebellum (CB) share basic molecular programs, but also form distinct spatial and functional subtypes. The regulatory epigenetic layers controlling such regional diversity have not been comprehensively investigated so far. Here, we present an integrated...

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Bibliographic Details
Published in:Glia 2021-09, Vol.69 (9), p.2160-2177
Main Authors: Welle, Anna, Kasakow, Carmen V., Jungmann, Annemarie M., Gobbo, Davide, Stopper, Laura, Nordström, Karl, Salhab, Abdulrahman, Gasparoni, Gilles, Scheller, Anja, Kirchhoff, Frank, Walter, Jörn
Format: Article
Language:English
Subjects:
Animals
Astrocytes
Astrocytes - metabolism
Cerebellum
Cerebellum - metabolism
Cerebral cortex
Cerebral Cortex - metabolism
Chromatin
chromatin accessibility
Combinatorial analysis
Cortex (temporal)
Deoxyribonucleic acid
development
DNA
DNA methylation
Epigenesis, Genetic - genetics
Epigenetics
Epigenomics
Forkhead Transcription Factors - genetics
Foxg1 protein
gene expression
Mice
Nerve Tissue Proteins - metabolism
Networks
Neurogenesis
regionalization
Transcription factors
Transcriptomes
Young adults
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Summary:Astrocytes from the cerebral cortex (CTX) and cerebellum (CB) share basic molecular programs, but also form distinct spatial and functional subtypes. The regulatory epigenetic layers controlling such regional diversity have not been comprehensively investigated so far. Here, we present an integrated epigenome analysis of methylomes, open chromatin, and transcriptomes of astroglia populations isolated from the cortex or cerebellum of young adult mice. Besides a basic overall similarity in their epigenomic programs, cortical astrocytes and cerebellar astrocytes exhibit substantial differences in their overall open chromatin structure and in gene‐specific DNA methylation. Regional epigenetic differences are linked to differences in transcriptional programs encompassing genes of region‐specific transcription factor networks centered around Lhx2/Foxg1 in CTX astrocytes and the Zic/Irx families in CB astrocytes. The distinct epigenetic signatures around these transcription factor networks point to a complex interconnected and combinatorial regulation of region‐specific transcriptomes. These findings suggest that key transcription factors, previously linked to temporal, regional, and spatial control of neurogenesis, also form combinatorial networks important for astrocytes. Our study provides a valuable resource for the molecular basis of regional astrocyte identity and physiology. Main Points The epigenomes of cortical and cerebellar astrocytes are highly distinct. We find an epigenetically primed network around the transcription factors Lhx2 and Foxg1 in cortical astrocytes, while Zic1/Zic4 form a network in cerebellar astrocytes.
ISSN:0894-1491
1098-1136
DOI:10.1002/glia.24016