Olig2 Targets Chromatin Remodelers to Enhancers to Initiate Oligodendrocyte Differentiation

Yu, Yang; Chen, Ying; Kim, BongWoo; Wang, Haibo; Zhao, Chuntao; He, Xuelian; Liu, Lei; Liu, Wei; Wu, Lai Man Natalie; Mao, Meng; Chan, Jonah R.; Wu, Jiang; Lü, Qing

doi:10.1016/j.cell.2012.12.006

Cited by 314 publications

(430 citation statements)

References 49 publications

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“…Both Brg1 and Baf155 heterozygous mutants exhibit neural tube closure defects and exencephaly, suggesting that BAF complexes have an important and dosage-sensitive role in neural differentiation and development (Bultman et al, 2000;Kim et al, 2001). In agreement with these observations, BRG1 is required during both neuronal and glial differentiation (Marathe et al, 2013;Matsumoto et al, 2006;Weider et al, 2012;Yu et al, 2013). In the central nervous system, the differentiation of glial progenitor cells to form first immature and subsequently mature myelinating oligodendrocytes requires BRG1 (Yu et al, 2013).…”

Section: Baf Complexes In Neural Developmentsupporting

confidence: 67%

ATP-dependent chromatin remodeling during mammalian development

2016

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Precise gene expression ensures proper stem and progenitor cell differentiation, lineage commitment and organogenesis during mammalian development. ATP-dependent chromatin-remodeling complexes utilize the energy from ATP hydrolysis to reorganize chromatin and, hence, regulate gene expression. These complexes contain diverse subunits that together provide a multitude of functions, from early embryogenesis through cell differentiation and development into various adult tissues. Here, we review the functions of chromatin remodelers and their different subunits during mammalian development. We discuss the mechanisms by which chromatin remodelers function and highlight their specificities during mammalian cell differentiation and organogenesis.

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Section: Baf Complexes In Neural Developmentsupporting

confidence: 67%

ATP-dependent chromatin remodeling during mammalian development

2016

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“…2-4, 6, 8). Since Olig2 overexpression in neural stem cells produces actively remyelinating OLs in vitro and in remyelination (Copray et al, 2006), and Olig2 is sufficient to initiate the OL differentiation program (Yu et al, 2013), it is possible that the induction of Olig2ϩ cells by Sox17 promoted the increase in CC1ϩ cells both during development and after lysolecithin-induced injury.…”

Section: Discussionmentioning

confidence: 99%

Transgenic Overexpression of Sox17 Promotes Oligodendrocyte Development and Attenuates Demyelination

Ming

Chew

Gallo

2013

Journal of Neuroscience

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We have previously demonstrated that Sox17 regulates cell cycle exit and differentiation in oligodendrocyte progenitor cells. Here we investigated its function in white matter (WM) development and adult injury with a newly generated transgenic mouse overexpressing Sox17 in the oligodendrocyte lineage under the CNPase promoter. Sox17 overexpression in CNP-Sox17 mice sequentially promoted postnatal oligodendrogenesis, increasing NG2 progenitor cells from postnatal day (P) 15, then O4ϩ and CC1ϩ cells at P30 and P120, respectively. Total Olig2ϩ oligodendrocyte lineage cells first decreased between P8 and P22 through Sox17-mediated increase in apoptotic cell death, and thereafter significantly exceeded WT levels from P30 when cell death had ceased. CNP-Sox17 mice showed increased Gli2 protein levels and Gli2ϩ cells in WM, indicating that Sox17 promotes the generation of oligodendrocyte lineage cells through Hedgehog signaling. Sox17 overexpression prevented cell loss after lysolecithin-induced demyelination by increasing Olig2ϩ and CC1ϩ cells in response to injury. Furthermore, Sox17 overexpression abolished the injury-induced increase in TCF7L2/TCF4ϩ cells, and protected oligodendrocytes from apoptosis by preventing decreases in Gli2 and Bcl-2 expression that were observed in WT lesions. Our study thus reveals a biphasic effect of Sox17 overexpression on cell survival and oligodendrocyte formation in the developing WM, and that its potentiation of oligodendrocyte survival in the adult confers resistance to injury and myelin loss. This study demonstrates that overexpression of this transcription factor might be a viable protective strategy to mitigate the consequences of demyelination in the adult WM.

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“…Although BRG1 was reported to interact functionally with TAL1 (32), we are unaware of examples of a mechanism requiring both BRG1 and LDB1. The BRG1 activity may have broad implications in diverse contexts, because BRG1 is required for Pax6-dependent control of neural fate (38), for Olig2 to establish an oligodendrocyte-specific transcriptional program (64), and for cardiovascular development (65,66).…”

Section: Discussionmentioning

confidence: 99%

Mechanism governing a stem cell-generating cis -regulatory element

Sanalkumar

Johnson

Gào

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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The unremitting demand to replenish differentiated cells in tissues requires efficient mechanisms to generate and regulate stem and progenitor cells. Although master regulatory transcription factors, including GATA binding protein-2 (GATA-2), have crucial roles in these mechanisms, how such factors are controlled in developmentally dynamic systems is poorly understood. Previously, we described five dispersed Gata2 locus sequences, termed the −77, −3.9, −2.8, −1.8, and +9.5 GATA switch sites, which contain evolutionarily conserved GATA motifs occupied by GATA-2 and GATA-1 in hematopoietic precursors and erythroid cells, respectively. Despite common attributes of transcriptional enhancers, targeted deletions of the −2.8, −1.8, and +9.5 sites revealed distinct and unpredictable contributions to Gata2 expression and hematopoiesis. Herein, we describe the targeted deletion of the −3.9 site and mechanistically compare the −3.9 site with other GATA switch sites. The −3.9 −/− mice were viable and exhibited normal Gata2 expression and steady-state hematopoiesis in the embryo and adult. We established a Gata2 repression/reactivation assay, which revealed unique +9.5 site activity to mediate GATA factor-dependent chromatin structural transitions. Loss-of-function analyses provided evidence for a mechanism in which a mediator of long-range transcriptional control [LIM domain binding 1 (LDB1)] and a chromatin remodeler [Brahma related gene 1 (BRG1)] synergize through the +9.5 site, conferring expression of GATA-2, which is known to promote the genesis and survival of hematopoietic stem cells.cis element | HSCs W hereas proximal promoter sequences assemble the basal transcriptional machinery and RNA polymerase, distant cis-regulatory elements often confer tissue-specific or contextdependent transcriptional regulation. Enhancer elements reside many kilobases upstream or downstream of a promoter or within introns, and extensive efforts have focused on elucidating "action-at-a-distance" mechanisms (1). Long-range transcriptional control involves physical interactions between proteins bound at distal regions and promoter sequences and higher order structural transitions, including subnuclear relocalization of target loci (2-4). Given the high frequency of long-range mechanisms at mammalian loci and the mutations that disrupt the function of such elements in pathological conditions, elucidating the underlying mechanisms in development,

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Olig2 Targets Chromatin Remodelers to Enhancers to Initiate Oligodendrocyte Differentiation

Cited by 314 publications

References 49 publications

ATP-dependent chromatin remodeling during mammalian development

ATP-dependent chromatin remodeling during mammalian development

Transgenic Overexpression of Sox17 Promotes Oligodendrocyte Development and Attenuates Demyelination

Mechanism governing a stem cell-generating cis -regulatory element

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