Li Huiliang, Lu Yan, Smith Hazel K, Richardson William D
Wolfson Institute for Biomedical Research and Department of Biology, University College London, London WC1E 6BT, United Kingdom.
J Neurosci. 2007 Dec 26;27(52):14375-82. doi: 10.1523/JNEUROSCI.4456-07.2007.
The oligodendrocyte lineage genes (Olig1/2), encoding basic helix-loop-helix transcription factors, were first identified in screens for master regulators of oligodendrocyte development. OLIG1 is important for differentiation of oligodendrocyte precursors into myelin-forming oligodendrocytes during development and is thought to play a crucial role in remyelination during multiple sclerosis. However, it is still unclear how OLIG1 interacts with its transcriptional cofactors and DNA targets. OLIG1 was reportedly restricted to mammals, but we demonstrate here that zebrafish and other teleosts also possess an OLIG1 homolog. In zebrafish, as in mammals, Olig1 is expressed in the oligodendrocyte lineage. Olig1 associates physically with another myelin-associated transcription factor, Sox10, and the Olig1/Sox10 complex activates mbp (myelin basic protein) transcription via conserved DNA sequence motifs in the mbp promoter region. In contrast, Olig2 does not bind to Sox10 in zebrafish, although both OLIG1 and OLIG2 bind SOX10 in mouse.
少突胶质细胞谱系基因(Olig1/2)编码碱性螺旋-环-螺旋转录因子,最初是在少突胶质细胞发育的主要调节因子筛选中被鉴定出来的。OLIG1对于少突胶质细胞前体在发育过程中分化为形成髓鞘的少突胶质细胞很重要,并且被认为在多发性硬化症的髓鞘再生中起关键作用。然而,目前尚不清楚OLIG1如何与其转录辅因子和DNA靶点相互作用。据报道,OLIG1仅限于哺乳动物,但我们在此证明斑马鱼和其他硬骨鱼也拥有OLIG1同源物。在斑马鱼中,与在哺乳动物中一样,Olig1在少突胶质细胞谱系中表达。Oligl与另一种髓鞘相关转录因子Sox10在物理上相互作用,并且Olig1/Sox10复合物通过mbp启动子区域中的保守DNA序列基序激活mbp(髓鞘碱性蛋白)转录。相比之下,在斑马鱼中Olig2不与Sox10结合,尽管在小鼠中OLIG1和OLIG2都与SOX10结合。