SBE6: a novel long-range enhancer involved in driving sonic hedgehog expression in neural progenitor cells.

SBE6: a novel long-range enhancer involved in driving sonic hedgehog expression in neural progenitor cells.
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DOI:
10.1098/rsob.160197
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发表时间:
2016-11
期刊:
影响因子:
5.8
通讯作者:
Bickmore WA
Bickmore WA
中科院分区:
生物学2区
文献类型:
--
作者:
Benabdallah NS;Gautier P;Hekimoglu-Balkan B;Lettice LA;Bhatia S;Bickmore WA

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在发育中起关键作用的基因的表达受到增强子介导的非常严格的空间和时间控制。一个经典的例子是音刺猬基因(Shh),它在体内和体外神经祖细胞的增殖,分化和存活中起着关键作用。Shh在大脑中的表达受到几种已知的增强子的严格控制,这些增强子已经通过遗传、基因组和功能测定鉴定。在胚胎干细胞分化为神经祖细胞的过程中使用染色质分析,在这里,我们报告了一种新的长距离增强子Shh-Shh-brain-enhancer-6(SBE 6)的鉴定,该增强子位于Shh上游100 kb处,并且在此分化程序中适当诱导Shh表达所需。该元件能够驱动脊椎动物大脑中的表达。我们的研究说明了如何染色质为重点的方法,再加上在体内测试,可用于确定新的细胞类型特异性顺式调节元件,并指出在胚胎脑发育过程中的Shh表达控制的进一步复杂性。
The expression of genes with key roles in development is under very tight spatial and temporal control, mediated by enhancers. A classic example of this is the sonic hedgehog gene (Shh), which plays a pivotal role in the proliferation, differentiation and survival of neural progenitor cells both in vivo and in vitro. Shh expression in the brain is tightly controlled by several known enhancers that have been identified through genetic, genomic and functional assays. Using chromatin profiling during the differentiation of embryonic stem cells to neural progenitor cells, here we report the identification of a novel long-range enhancer for Shh—Shh-brain-enhancer-6 (SBE6)—that is located 100 kb upstream of Shh and that is required for the proper induction of Shh expression during this differentiation programme. This element is capable of driving expression in the vertebrate brain. Our study illustrates how a chromatin-focused approach, coupled to in vivo testing, can be used to identify new cell-type specific cis-regulatory elements, and points to yet further complexity in the control of Shh expression during embryonic brain development.
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