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Highly specific interactions between bHLH transcription factors and chromatin during retina development.

机译:视网膜发育过程中bHLH转录因子和染色质之间的高度特异性相互作用。

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Basic helix-loop-helix (bHLH) transcription factors such as atonal homolog 5 (ATH5) and neurogenin 2 (NGN2) determine crucial events in retinogenesis. Using chromatin immunoprecipitation, we demonstrate that their interactions with target promoters undergo dynamic changes as development proceeds in the chick embryo. Chick ATH5 associates with its own promoter and with the promoter of the beta3 nicotinic receptor specifically in retinal ganglion cells and their precursors. NGN2 binds to the ATH5 promoter in retina but not in optic tectum, suggesting that interactions between bHLH factors and chromatin are highly tissue specific. The transcriptional activations of both promoters correlate with dimethylation of lysine 4 on histone H3. Inactivation of the ATH5 promoter in differentiated neurons is accompanied by replication-independent chromatin de-methylation. This report is one of the first demonstrations of correlation between gene expression, binding of transcription factors and chromatin modification in a developing neural tissue.
机译:基本的螺旋-环-螺旋(bHLH)转录因子,如无调子同源物5(ATH5)和神经生成素2(NGN2),决定了视网膜发生中的关键事件。使用染色质免疫沉淀,我们证明了它们与目标启动子的相互作用随着发育在雏鸡胚胎中发生动态变化。小鸡ATH5与其自身的启动子以及β3烟碱样受体的启动子相关联,特别是在视网膜神经节细胞及其前体中。 NGN2结合视网膜中的ATH5启动子,但不结合视锥细胞,这表明bHLH因子与染色质之间的相互作用具有高度组织特异性。两个启动子的转录激活与组蛋白H3上赖氨酸4的二甲基化相关。分化神经元中ATH5启动子的失活伴随着复制非依赖性染色质去甲基化。该报告是发育中的神经组织中基因表达,转录因子结合和染色质修饰之间相关性的首批证明之一。

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