Le Douarin B, Nielsen A L, Garnier J M, Ichinose H, Jeanmougin F, Losson R, Chambon P
Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS/INSERM/ULP, Collège de France, Illkirch, France.
EMBO J. 1996 Dec 2;15(23):6701-15.
Nuclear receptors (NRs) are ligand-inducible transcription factors that mediate complex effects on development, differentiation and homeostasis. They regulate the transcription of their target genes through binding to cognate DNA sequences as homodimers or heterodimers. The molecular mechanisms underlying transcriptional activation by NRs are still poorly understood, although intermediary factors (mediators) appear to be involved in mediating the transactivation functions of NRs. TIF1 has been identified previously as a protein that interacts specifically with the ligand binding domain of several nuclear receptors, both in yeast and in vitro. The characteristics of these interactions have led us to suggest that TIF1 might be a mediator of the NR ligand-inducible activation function AF-2. Using a two-hybrid screening in yeast, we have now identified two TIF1-binding proteins, mHP1 alpha and mMOD1, that are mouse homologues of the Drosophila heterochromatinic protein 1. Using mHP1 alpha as a bait in a second two-hybrid screening, we have isolated cDNAs encoding proteins that are also very likely to be involved in chromatin structure and function, as well as a protein structurally and functionally related to TIF1 (renamed TIF1 alpha), which was named TIF1 beta. Here we discuss how the function of members of the TIF1 family in the control of transcription could be exerted at the level of the structure of the chromatin template.
核受体（NRs）是配体诱导型转录因子，介导对发育、分化和体内平衡的复杂影响。它们通过以同二聚体或异二聚体形式结合同源DNA序列来调节其靶基因的转录。尽管中间因子（介质）似乎参与介导核受体的反式激活功能，但核受体转录激活的分子机制仍知之甚少。TIF1先前已被鉴定为一种在酵母和体外均能与几种核受体的配体结合域特异性相互作用的蛋白质。这些相互作用的特性使我们推测TIF1可能是核受体配体诱导激活功能AF-2的介质。利用酵母双杂交筛选，我们现已鉴定出两种TIF1结合蛋白，即mHP1α和mMOD1，它们是果蝇异染色质蛋白1的小鼠同源物。在第二次双杂交筛选中，以mHP1α为诱饵，我们分离出了编码很可能也参与染色质结构和功能的蛋白质的cDNA，以及一种在结构和功能上与TIF1相关的蛋白质（重新命名为TIF1α），它被命名为TIF1β。在此我们讨论TIF1家族成员在转录调控中的功能如何在染色质模板结构水平上发挥作用。
