Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Seh1 Interacts with Olig2 and Brd7 to Promote Oligodendrocyte Differentiation and Myelination (ChIP-Seq)

ABSTRACT: Nuclear pore complex components (Nups) are involved in neural development and alterations in Nup genes are linked to human neurological diseases. However, the physiological functions of specific Nups and the underlying mechanisms involved in these processes remain elusive. Here we show that tissue-specific depletion of nucleoporin Seh1 causes dramatic myelination defects in the Central Nervous System (CNS). Seh1-deficient Oligodendrocyte Progenitor Cells (OPCs) proliferate properly, but 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 depletion of Seh1 alters open chromatin configurations at its target genes. Mechanistically, Seh1 regulates OPCs differentiation by assembling Olig2 and Brd7 into a transcription complex at nuclear pores. Together, our results reveal that Seh1 is required for oligodendrocyte differentiation and myelination by promoting assembly of an Olig2-dependent transcription complex and expose nucleoporins as key players in the CNS.

ORGANISM(S): Rattus norvegicus

PROVIDER: GSE119814 | GEO | 2018/09/12

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Seh1 Interacts with Olig2 and Brd7 to Promote Oligodendrocyte Differentiation and Myelination (ATAC_Seq)

Project description:Nuclear pore complex components (Nups) are involved in neural development and alterations in Nup genes are linked to human neurological diseases. However, the physiological functions of specific Nups and the underlying mechanisms involved in these processes remain elusive. Here we show that tissue-specific depletion of nucleoporin Seh1 causes dramatic myelination defects in the Central Nervous System (CNS). Seh1-deficient Oligodendrocyte Progenitor Cells (OPCs) proliferate properly, but 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 depletion of Seh1 alters open chromatin configurations at its target genes. Mechanistically, Seh1 regulates OPCs differentiation by assembling Olig2 and Brd7 into a transcription complex at nuclear pores. Together, our results reveal that Seh1 is required for oligodendrocyte differentiation and myelination by promoting assembly of an Olig2-dependent transcription complex and expose nucleoporins as key players in the CNS.

2018-09-12 | GSE119815 | GEO

Seh1 Interacts with Olig2 and Brd7 to Promote Oligodendrocyte Differentiation and Myelination (RNA-Seq)

2018-09-12 | GSE119812 | GEO

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

Project description:Seh1 Interacts with Olig2 and Brd7 to Promote Oligodendrocyte Differentiation and Myelination

| PRJNA490362 | ENA

Seh1 Interacts with Olig2 and Brd7 to Promote Oligodendrocyte Differentiation and Myelination (ATAC_Seq)

Project description:Seh1 Interacts with Olig2 and Brd7 to Promote Oligodendrocyte Differentiation and Myelination (ATAC_Seq)

| PRJNA490366 | ENA

Seh1 Interacts with Olig2 and Brd7 to Promote Oligodendrocyte Differentiation and Myelination (RNA-Seq)

Project description:Seh1 Interacts with Olig2 and Brd7 to Promote Oligodendrocyte Differentiation and Myelination (RNA-Seq)

| PRJNA490360 | ENA

Seh1 Interacts with Olig2 and Brd7 to Promote Oligodendrocyte Differentiation and Myelination (ChIP-Seq)

Project description:Seh1 Interacts with Olig2 and Brd7 to Promote Oligodendrocyte Differentiation and Myelination (ChIP-Seq)

| PRJNA490364 | ENA

Genome-wide mapping of Olig2 targets in primary oligodendrocytes

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/?-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 ?-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. ChIP-seq was performed to identify Olig2 direct target genes in oligodendrocytes during oligodendrocyte differentiation.

2012-08-31 | E-GEOD-40506 | 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

Candidate pathways for promoting differentiation and quiescence of oligodendrocyte progenitor-like cells in glioblastoma

Project description:The mature CNS contains PDGFRA+ ‘oligodendrocyte progenitor cells’ (OPC) which may remain quiescent, proliferate, or differentiate into oligodendrocytes. In human gliomas, rapidly proliferating Olig2+ cells resembling OPCs are frequently observed. We sought to identify, in vivo, candidate pathways uniquely required for OPC differentiation or quiescence. Using the bacTRAP methodology, we generated and analyzed mouse lines for translational profiling the major cells types (including OPCs), in the normal mouse brain. We then profiled oligodendoglial (Olig2+) cells from a mouse model of Pdgf-driven glioma. This analysis confirmed that Olig2+ tumor cells are most similar to OPCs, yet, it identified differences in key progenitor genes - candidates for promotion of differentiation or quiescence.

2012-10-04 | GSE30626 | GEO

Identification of genome-wide targets of Olig2 in the adult mouse spinal cord using ChIP-Seq

Project description:Olig2 is a crucial factor in the specification and differentiation of oligodendrocyte precursor cells that give rise to mature, myelin-producing OLs in the developing and postnatal CNS; however, its role in adulthood is less well understood. To investigate the role Olig2 plays in regulating gene expression in the adult oligodendrocyte lineage in a physiologically-relevant context, we performed chromatin immunoprecipitation followed by next generation sequencing analysis using whole spinal cord tissue harvested from adult mice. We found that many of the Olig2-bound sites were associated with genes with biological processes corresponding to myelination and ensheathment, as well as cell cycle and cytoskeletal regulation, suggesting Olig2 continues to play a critical role in processes related to OL differentiation and myelination well into adulthood.

2017-10-20 | GSE103324 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data