Genomics

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Genome-wide mapping of Olig2 targets in primary oligodendrocytes


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

ORGANISM(S): Rattus norvegicus  

SUBMITTER: Qing R Lu   Qing Richard Lu 

PROVIDER: E-GEOD-40506 | ArrayExpress | 2012-08-31

SECONDARY ACCESSION(S): SRP015333GSE40506PRJNA174195

REPOSITORIES: GEO, ArrayExpress, ENA

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Publications

Dual-mode modulation of Smad signaling by Smad-interacting protein Sip1 is required for myelination in the central nervous system.

Weng Qinjie Q   Chen Ying Y   Wang Haibo H   Xu Xiaomei X   Yang Bo B   He Qiaojun Q   Shou Weinian W   Chen Yan Y   Higashi Yujiro Y   van den Berghe Veronique V   Seuntjens Eve E   Kernie Steven G SG   Bukshpun Polina P   Sherr Elliott H EH   Huylebroeck Danny D   Lu Q Richard QR  

Neuron 20120201 4


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 prot  ...[more]

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