Scaffold attachment factor B1 directly interacts with nuclear receptors in living cells and represses transcriptional activity
Scaffold attachment factor B1 directly interacts with nuclear receptors in living cells and represses transcriptional activity
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DOI：
10.1677/jme.1.01856
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发表时间：
2005-12-01
影响因子：
3.5
通讯作者：
Gelman, L
中科院分区：
文献类型：
--
作者：
Debril, MB;Dubuquoy, L;Gelman, L
转录活性依赖于改变染色质结构的辅助调节因子，并充当转录因子和基础转录机制之间的桥梁因子。以人过氧化物酶体增殖物激活受体γ(PPARγ)的DE结构域为诱饵，在酵母双杂交筛选人脂肪组织文库中分离到支架附着因子B1(SAFB1/HET/HAP)，它是雌激素受体α的辅阻遏子。我们发现SAFB1在人类中有非常广泛的组织表达谱，在小鼠胚胎发育过程中也一直有表达。SAFB1在下拉试验中不仅与PPAR伽马相互作用，而且还与迄今测试的所有核受体相互作用，尽管亲和力不同。活细胞中的荧光共振能量转移(FRET)实验进一步证明了SAFB1和PPARγ在体内的关联。最后，我们证明SAFB1是一种相当普遍的核受体辅阻遏子。它在脂肪细胞和肠细胞分化早期的表达变化表明SAFB1可能影响细胞的增殖和分化决定。
Transcriptional activity relies on coregulators that modify the chromatin structure and serve as bridging factors between transcription factors and the basal transcription machinery. Using the DE domain of human peroxisome proliferator-activated receptor gamma (PPAR gamma) as bait in a yeast two-hybrid screen of a human adipose tissue library, we isolated the scaffold attachment factor B1 (SAFB1/HET/HAP), which was previously shown to be a corepressor of estrogen receptor alpha. We show here that SAFB1 has a very broad tissue expression profile in human and is also expressed all along mouse embryogenesis. SAFB1 interacts in pull-down assays not only with PPAR gamma but also with all nuclear receptors tested so far, albeit with different affinities. The association of SAFB1 and PPAR gamma in vivo is further demonstrated by fluorescence resonance energy transfer (FRET) experiments in living cells. We finally show that SAFB1 is a rather general corepressor for nuclear receptors. Its change in expression during the early phases of adipocyte and enterocyte differentiation suggests that SAFB1 potentially influences cell proliferation and differentiation decisions.