Novel transcription factor Satb2 interacts with matrix attachment region DNA elements in a tissue-specific manner and demonstrates cell-type-dependent expression in the developing mouse CNS

Novel transcription factor Satb2 interacts with matrix attachment region DNA elements in a tissue-specific manner and demonstrates cell-type-dependent expression in the developing mouse CNS
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DOI:
10.1111/j.1460-9568.2005.03897.x
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发表时间:
2005-02-01
影响因子:
3.4
通讯作者:
Tarabykin, V
Tarabykin, V
中科院分区:
医学3区
文献类型:
--
作者:
Britanova, O;Akopov, S;Tarabykin, V

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Satb1是一种新型的第一种细胞类型特异性转录因子,它作为大染色质结构域转录的调节因子发挥作用。我们在寻找控制神经分化的基因的cDNA消减筛选中鉴定出了Satb1的一个紧密同源物Satb2。Satb2与Satb1有61%的氨基酸同源性。在发育中的小鼠中枢神经系统的不同细胞亚群中,Satb2和Satb1的表达以相互排斥的方式被检测到。在电泳迁移率变动分析中,我们证明来自胚胎第18.5天小鼠发育中的新皮质的核提取物(与基底神经节相反)含有一种能与基质附着区DNA元件(MARs)高亲和力相互作用的蛋白质复合物。内源性Satb2蛋白是该复合物的一部分。在发育中的新皮质中,Satb2主要在表层被检测到。在发育中的脊髓中,Satb2的表达标志着背侧Lbx1阳性神经元的一个亚群和腹侧Isl1阳性神经元的一个亚群。在Lbx1突变体中,Satb2的表达大幅降低。我们认为Satb2可能通过与MARs结合在高阶染色质结构水平上调节神经元亚群的分化。
Satb1 is a first cell-type-specific transcription factor of a novel type that functions as a regulator of the transcription of large chromatin domains. We identified a close homologue of Satb1, Satb2, in a cDNA subtraction screening in a search for genes controlling neural differentiation. Satb2 showed 61% amino-acid homology to Satb1. Satb2 and Satb1 expression was detected in different cell subpopulations of developing mouse CNS in a mutually exclusive manner. In the electrophoretic mobility shift assay we demonstrate that nuclear extracts from the embryonic day 18.5 mouse developing neocortex, in contrast to basal ganglia, contain a protein complex interacting with matrix attachment region DNA elements (MARs) with high affinity. Endogenous Satb2 protein is a part of this complex. In the developing neocortex Satb2 was detected largely in the superficial layers. In the developing spinal cord Satb2 expression marks a subpopulation of Lbx1-positive neurons dorsally and a subgroup of Isl1-positive neurons ventrally. In the Lbx1 mutants Satb2 expression is greatly reduced. We suggest that Satb2 may regulate differentiation of subsets of neurons at the level of higher order chromatin structure via binding to MARs.