Interaction with members of the heterochromatin protein 1 (HP1) family and histone deacetylation are differentially involved in transcriptional silencing by members of the TIF1 family
Interaction with members of the heterochromatin protein 1 (HP1) family and histone deacetylation are differentially involved in transcriptional silencing by members of the TIF1 family
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DOI：
10.1093/emboj/18.22.6385
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发表时间：
1999-11-15
期刊：
影响因子：
11.4
通讯作者：
Losson, R
中科院分区：
文献类型：
--
作者：
Nielsen, AL;Ortiz, JA;Losson, R
哺乳动物TIF 1 α和TIF 1 β（KAP-1/KRIP-1）是具有内在沉默活性的相关转录中介因子。TIF 1 α被认为是配体核受体的常染色质靶点，而TIF 1 β可能作为含KRAB结构域的锌指蛋白大家族的共阻遏物。在这里，我们报告的协会TIF 1 β与异染色质和常染色质在间期核。核提取物的免疫共沉淀表明，内源性TIF 1 β（而不是TIF 1 α）与异染色质蛋白1（HPL）家族的成员相关。然而，在体外，TIF 1 α和TIF 1 β都与HP 1蛋白相互作用并使其磷酸化。这种相互作用涉及一个保守的氨基酸基序，这是至关重要的沉默活性的TIF 1 β，但不是TIF 1 α，我们进一步表明，阿司他汀ii，抑制剂组蛋白脱乙酰酶，可以干扰TIF 1和HP 1沉默。TIF 1 α的沉默活性似乎主要由组蛋白脱乙酰化引起，而TIF 1 β的沉默活性可能通过HP 1结合和组蛋白脱乙酰化两者介导。
Mammalian TIF1 alpha and TIF1 beta (KAP-1/KRIP-1) are related transcriptional intermediary factors that possess intrinsic silencing activity. TIF1 alpha is believed to be a euchromatic target for liganded nuclear receptors, while TIF1 beta may serve as a co-repressor for the large family of KRAB domain-containing zinc finger proteins. Here, we report an association of TIF1 beta with both heterochromatin and euchromatin in interphase nuclei. Co-immunoprecipitation of nuclear extracts shows that endogenous TIF1 beta, but not TIF1 alpha, is associated with members of the heterochromatin protein 1 (HPL) family. However, in vitro, both TIF1 alpha and TIF1 beta interact with and phosphorylate the HP1 proteins. This interaction involves a conserved amino acid motif, which is critical for the silencing activity of TIF1 beta but not TIF1 alpha, We further show that trichostatin ii, an inhibitor of histone deacetylases, can interfere with both TIF1 and HP1 silencing. The silencing activity of TIF1 alpha appears to result chiefly from histone deacetylation, whereas that of TIF1 beta may be mediated via both HP1 binding and histone deacetylation.