Differential deployment of REST and CoREST promotes glial subtype specification and oligodendrocyte lineage maturation.
Differential deployment of REST and CoREST promotes glial subtype specification and oligodendrocyte lineage maturation.
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DOI：
10.1371/journal.pone.0007665
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发表时间：
2009-11-03
期刊：
影响因子：
3.7
通讯作者：
Mehler MF
中科院分区：
文献类型：
--
作者：
Abrajano JJ;Qureshi IA;Gokhan S;Zheng D;Bergman A;Mehler MF
抑制因子-1 （RE1）沉默转录因子/神经元限制性沉默因子（REST/NRSF）是一种主要的转录调节因子，与许多基因组RE1位点结合，在那里它作为分子支架动态募集调节和表观遗传辅助因子，包括元件-1沉默转录因子（CoREST）的辅抑制因子。CoREST还作为各种辅助因子的中枢，在表观遗传重塑和转录调控中发挥重要作用。虽然REST可以将CoREST招募到其大分子复合物中，但CoREST复合物也独立于REST在基因组位点起作用。REST和CoREST具有广泛的上下文特异性功能，包括抑制神经干细胞（NSCs）和其他非神经元细胞中的神经元分化基因以及促进神经发生。尽管REST和CoREST参与神经元发育的多个方面，但它们在神经胶质细胞成熟中没有任何直接的调节作用。我们通过首次研究REST和CoREST在nsc介导的胶质细胞谱系规范和分化中的作用，挑战了这一观点。利用芯片上芯片（ChIP- ChIP）技术，我们确定了星形胶质细胞（AS）和少突胶质细胞（OL）谱系规范和OL谱系成熟和髓鞘形成过程中REST和CoREST靶基因的不同但重叠的发育阶段特异性谱，包括许多先前未涉及胶质细胞生物学或与REST和CoREST调控相关的基因。这些因子包括与大胶质细胞（AS和OL）的识别、成熟和维持有关的因子，如关键发育信号通路的成员和组合转录因子编码。我们的研究结果表明，REST和CoREST不仅调节神经元，还调节神经胶质谱系的发育。因此，这些因素可能介导关键的发育过程，包括神经发生和胶质发生的耦合以及神经元-胶质相互作用，这些相互作用是健康和特定神经疾病状态下突触和神经网络可塑性和内稳态的基础。
The repressor element-1 (RE1) silencing transcription factor/neuron-restrictive silencer factor (REST/NRSF) is a master transcriptional regulator that binds to numerous genomic RE1 sites where it acts as a molecular scaffold for dynamic recruitment of modulatory and epigenetic cofactors, including corepressor for element-1-silencing transcription factor (CoREST). CoREST also acts as a hub for various cofactors that play important roles in epigenetic remodeling and transcriptional regulation. While REST can recruit CoREST to its macromolecular complex, CoREST complexes also function at genomic sites independently of REST. REST and CoREST perform a broad array of context-specific functions, which include repression of neuronal differentiation genes in neural stem cells (NSCs) and other non-neuronal cells as well as promotion of neurogenesis. Despite their involvement in multiple aspects of neuronal development, REST and CoREST are not believed to have any direct modulatory roles in glial cell maturation. We challenged this view by performing the first study of REST and CoREST in NSC-mediated glial lineage specification and differentiation. Utilizing ChIP on chip (ChIP-chip) assays, we identified distinct but overlapping developmental stage-specific profiles for REST and CoREST target genes during astrocyte (AS) and oligodendrocyte (OL) lineage specification and OL lineage maturation and myelination, including many genes not previously implicated in glial cell biology or linked to REST and CoREST regulation. Amongst these factors are those implicated in macroglial (AS and OL) cell identity, maturation, and maintenance, such as members of key developmental signaling pathways and combinatorial transcription factor codes. Our results imply that REST and CoREST modulate not only neuronal but also glial lineage elaboration. These factors may therefore mediate critical developmental processes including the coupling of neurogenesis and gliogenesis and neuronal-glial interactions that underlie synaptic and neural network plasticity and homeostasis in health and in specific neurological disease states.
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影响因子：
4.8
作者：
Chakrabarti, SK;James, JC;Mirmira, RG
通讯作者：
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影响因子：
4.2
作者：
Campuzano, O.;Castillo-Ruiz, M. M.;Gonzalez, B.
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DOI：
10.1073/pnas.0401827101
发表时间：
2004-07-13
影响因子：
11.1
作者：
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