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SRF transcriptionally regulates the oligodendrocyte cytoskeleton during CNS myelination (ChIP-Seq)

ABSTRACT: SRF transcriptionally regulates the oligodendrocyte cytoskeleton during CNS myelination (ChIP-Seq)

PROVIDER: PRJNA1008703 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR25749500.fastq.gz	Fastqsanger.gz
	SRR25749501.fastq.gz	Fastqsanger.gz
	SRR25749502.fastq.gz	Fastqsanger.gz
	SRR25749503.fastq.gz	Fastqsanger.gz
	SRR25749504.fastq.gz	Fastqsanger.gz

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SRF transcriptionally regulates the oligodendrocyte cytoskeleton during CNS myelination

Project description:SRF transcriptionally regulates the oligodendrocyte cytoskeleton during CNS myelination

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Project description:SRF transcriptionally regulates the oligodendrocyte cytoskeleton during CNS myelination (RNA-Seq)

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SRF transcriptionally regulates the oligodendrocyte cytoskeleton during CNS myelination (snRNA-Seq)

Project description:Myelination of neuronal axons is essential for nervous system development. Myelination requires dramatic cytoskeletal dynamics in oligodendrocytes, but how actin is regulated during myelination is poorly understood. We recently identified serum response factor (SRF)—a transcription factor known to regulate expression of actin and actin regulators in other cell types—as a critical driver of myelination in the aged brain. Yet, a major gap remains in understanding the fundamental role of SRF in oligodendrocyte lineage cells. Here we show that SRF is required cell autonomously in oligodendrocytes for myelination during development. Combining ChIP-seq with RNA-seq identifies SRF-target genes in OPCs and oligodendrocytes that include actin and other key cytoskeletal genes. Accordingly, SRF knockout oligodendrocytes exhibit dramatically reduced actin filament levels early in differentiation, consistent with its role in actin-dependent myelin sheath initiation. Together, our findings identify SRF as a transcriptional regulator that controls the expression of cytoskeletal genes required in oligodendrocytes for myelination. This study identifies a novel pathway regulating oligodendrocyte biology with high relevance to brain development, aging, and disease.

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Genome-wide maps of Wnt effector Tcf7l2/Tcf4 occupancy in oligodendrocyte during CNS myelination

Project description:We performed genome-wide profiling of Tcf7l2 occupancy during oligodendrocyte differentiation and identified the key enzymes involved in cholesterol metabolism and essential for CNS myelination. Examination of Tcf7l2 chIP-seq in oligodendrocyte progenitor cell and 2 differentiation oligodendrocytes.

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Project description:Citrullination, the deimination of arginine residues into citrulline, has been implicated in the aetiology of several diseases. In multiple sclerosis (MS), citrullination is thought to be a major driver of pathology, through hypercitrullination and destabilization of myelin. As such, inhibition of citrullination has been suggested as a therapeutical strategy for MS. Here we show that citrullination by peptidylarginine deiminase 2 (PADI2) is in contrast required for normal oligodendrocyte differentiation, myelination and motor function. We identify several targets for PADI2, including not only myelin-related proteins, but also several chromatin-associated proteins, implicating PADI2 in epigenetic regulation. Accordingly, we observe that PADI2 inhibition and its knockdown affect chromatin accessibility and prevent the upregulation of genes involved in oligodendrocyte differentiation. Moreover, mice lacking PADI2, display motoric dysfunction and a decreased number of myelinated axons in the corpus callosum. Our study demonstrates that citrullination is required for oligodendrocyte lineage progression and myelination and thus its targeted activation in the oligodendrocyte lineage might be beneficial in the context of remyelination in diseases as MS.

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Oligodendrocyte intrinsic miR-27a controls myelination and remyelination

Project description:Oligodendrocyte intrinsic miR-27a controls myelination and remyelination

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