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Activation of the chromatin-remodeling factor Smarca4/Brg1 cooperates with Olig2 to establish oligodendrocyte identity and control CNS myelination [RNA-seq]

ABSTRACT: Spinal cord mRNA profiles of 14-day-old control (Brg1c/+;Olig1-Cre) and Smarca4/Brg1 conditional knockout (Brg1c/c;Olig1-Cre) mice were generated by RNA-seq. Differential expressed genes are identified using Cuffdiff and validated with qPCR. Spinal cord mRNA profiles of 14-day old control and Brg1c/c;Olig1-Cre mice were generated by RNA-sequencing.

ORGANISM(S): Mus musculus

SUBMITTER: Yang Yu

PROVIDER: E-GEOD-42443 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Olig2 targets chromatin remodelers to enhancers to initiate oligodendrocyte differentiation.

Yu Yang Y Chen Ying Y Kim Bongwoo B Wang Haibo H Zhao Chuntao C He Xuelian X Liu Lei L Liu Wei W Wu Lai Man N LM Mao Meng M Chan Jonah R JR Wu Jiang J Lu Q Richard QR

Cell 20130101 1-2

Establishment of oligodendrocyte identity is crucial for subsequent events of myelination in the CNS. Here, we demonstrate that activation of ATP-dependent SWI/SNF chromatin-remodeling enzyme Smarca4/Brg1 at the differentiation onset is necessary and sufficient to initiate and promote oligodendrocyte lineage progression and maturation. Genome-wide multistage studies by ChIP-seq reveal that oligodendrocyte-lineage determination factor Olig2 functions as a prepatterning factor to direct Smarca4/Br ...[more]

PMID: 23332759

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Activation of the chromatin-remodeling factor Smarca4/Brg1 cooperates with Olig2 to establish oligodendrocyte identity and control CNS myelination [RNA-seq]

Project description:Spinal cord mRNA profiles of 14-day-old control (Brg1c/+;Olig1-Cre) and Smarca4/Brg1 conditional knockout (Brg1c/c;Olig1-Cre) mice were generated by RNA-seq. Differential expressed genes are identified using Cuffdiff and validated with qPCR.

2013-01-20 | GSE42443 | GEO

Activation of the chromatin-remodeling factor Smarca4/Brg1 cooperates with Olig2 to establish oligodendrocyte identity and control CNS myelination [ChIP-seq]

Project description:We investigate the role of Brg1 and Olig2 during oligodendrocyte differentiation by combining gene conditional knockout and next generation sequencing technology. We generate genome-wide maps of RNA polymerase II (RPolII), Brg1 (Smarca4), Olig2 and histone modifications in primary rat oligodendrocyte precursor cells (iOLs), differentiating oligodendrocytes and mature oligodendrocytes.We found that Brg1 is intensely regulated by RPolII at the initiation of oligodedrocyte differentiation. The genomic distribution of Brg1 in differentiating oligodendrocytes is pre-directed by Olig2 in iOLs. The dynamic interaction of Brg1 and chromatin is correlate with the distinct stages of gene expression during maturation. Finally, we show that Brg1 and Olig2 localization predict critical genes controling CNS myeliantion. Our study represents the first detailed analysis of genomic landscape during the oligodendrocyte development and provides a framework for further understanding of molecular mechanisms underlying oligodendrocyte lineage progression. Genomic distribution of Brg1, Olig2, RPolII and three different histone modifications in three oligodendrocyte developemtal stages were examined using primary cells by ChIP-sequencing. Spinal cord mRNA profiles of 14-day old control and Brg1c/c;Olig1-Cre mice were generated by RNA-sequencing.

2013-01-20 | E-GEOD-42447 | biostudies-arrayexpress

Activation of the chromatin-remodeling factor Smarca4/Brg1 cooperates with Olig2 to establish oligodendrocyte identity and control CNS myelination [ChIP-seq]

2013-01-20 | GSE42447 | GEO

Activation of the chromatin-remodeling factor Smarca4/Brg1 cooperates with Olig2 to establish oligodendrocyte identity and control CNS myelination

Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

2013-01-20 | E-GEOD-42454 | biostudies-arrayexpress

Expression data from Sip1 cKO and control mice spinal cord

Project description:Myelination by oligodendrocytes in the central nervous system (CNS) is essential for proper brain function, yet the molecular determinants that control this process remain poorly understood. The basic helix-loop-helix transcription factors Olig1 and Olig2 promote myelination, whereas bone morphogenetic protein (BMP) and Wnt/β-catenin signaling inhibit myelination. Here we show that these opposing regulators of myelination are functionally linked by the Olig1/2 common target Smad-interacting protein-1 (Sip1). We demonstrate that Sip1 is an essential modulator of CNS myelination. Sip1 represses differentiation inhibitory signals by antagonizing BMP receptor-activated Smad activity while activating crucial oligodendrocyte-promoting factors. Importantly, a key Sip1-activated target, Smad7, is required for oligodendrocyte differentiation and partially rescues differentiation defects caused by Sip1 loss. Smad7 promotes myelination by blocking the BMP- and β-catenin-negative regulatory pathways. Thus, our findings reveal that Sip1-mediated antagonism of inhibitory signaling is critical for promoting CNS myelination and point to new mediators for myelin repair. We carried out microarray profiling analysis in the Sip1 conditional KO (cKO) mouse spinal cord to detail the change of global gene expression. Sip1 c/c;Olig1-Cre mouse spinal cord was collected at P14 for RNA extraction and Affymetrix microarray analysis. Sip1 c/+;Olig1-Cre littermate spinal cord was used as the control.

2012-08-31 | E-GEOD-40510 | biostudies-arrayexpress

Activation of the chromatin-remodeling factor Smarca4/Brg1 cooperates with Olig2 to establish oligodendrocyte identity and control CNS myelination

Project description:This SuperSeries is composed of the SubSeries listed below.

2013-01-20 | GSE42454 | GEO

Quantitative Analysis of Wild Type and Secisbp2l Conditional Knockout Spinal Cord Transcriptomes

Project description:The goals of this study are to analyze NGS-derived spinal cord transcriptome profiling (RNA-seq) of wild type (WT) and Olig1-Cre mediated Secisbp2l Exon3 deletion (cKO) at postnatal day 7 (P7). Spinal cord RNA profiles were generated by deep sequencing, using Illumina Hiseq 2500. The sequence reads that passed quality filters were analyzed at the transcript isoform level with HISAT2 and RSeQC.

2019-08-31 | GSE119359 | GEO

Nucleoporin Seh1 Interacts with Olig2/Brd7 to Promote Oligodendrocyte Differentiation and Myelination.

Project description:Nucleoporins (Nups) are involved in neural development, and alterations in Nup genes are linked to human neurological diseases. However, physiological functions of specific Nups and the underlying mechanisms involved in these processes remain elusive. Here, we show that tissue-specific depletion of the nucleoporin Seh1 causes dramatic myelination defects in the CNS. Although proliferation is not altered in Seh1-deficient oligodendrocyte progenitor cells (OPCs), they fail to differentiate into mature oligodendrocytes, which impairs myelin production and remyelination after demyelinating injury. Genome-wide analyses show that Seh1 regulates a core myelinogenic regulatory network and establishes an accessible chromatin landscape. Mechanistically, Seh1 regulates OPCs differentiation by assembling Olig2 and Brd7 into a transcription complex at nuclear periphery. Together, our results reveal that Seh1 is required for oligodendrocyte differentiation and myelination by promoting assembly of an Olig2-dependent transcription complex and define a nucleoporin as a key player in the CNS.

| S-EPMC6508993 | biostudies-literature

Divergent transcriptional regulation of astrocyte reactivity across disorders [TR_ATAC_SCI]

Project description:Single-nuclei Assay for Transposase-Accessible Chromatin with sequencing (snATACseq) was applied to examine chromatin landscape changes and transcriptional regulator (TR) DNA motif accessibility in reactive astrocytes following traumatic spinal cord injury (SCI). Astrocyte nuclei were isolated from the spinal cord of wild type mice and mice with astrocyte-specific conditional gene deletion (cKO) of test-case TRs, SMARCA4 (Smarca4-astro-cKO) or STAT3 knockout (Stat3-astro-cKO). Comparison of differential chromatin accessibility revealed substantial remodeling during astrocyte reactivity, with more chromatin opening than closing. Marked alterations in access to SCI reactivity-associated TR motifs were also detected.

2022-05-26 | GSE199481 | GEO

Seh1 Interacts with Olig2 and Brd7 to Promote Oligodendrocyte Differentiation and Myelination

Project description:This SuperSeries is composed of the SubSeries listed below.

2018-09-12 | GSE119816 | GEO