The FANTOM Consortium, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA.
Cell. 2010 Mar 5;140(5):744-52. doi: 10.1016/j.cell.2010.01.044.
Combinatorial interactions among transcription factors are critical to directing tissue-specific gene expression. To build a global atlas of these combinations, we have screened for physical interactions among the majority of human and mouse DNA-binding transcription factors (TFs). The complete networks contain 762 human and 877 mouse interactions. Analysis of the networks reveals that highly connected TFs are broadly expressed across tissues, and that roughly half of the measured interactions are conserved between mouse and human. The data highlight the importance of TF combinations for determining cell fate, and they lead to the identification of a SMAD3/FLI1 complex expressed during development of immunity. The availability of large TF combinatorial networks in both human and mouse will provide many opportunities to study gene regulation, tissue differentiation, and mammalian evolution.
转录因子之间的组合相互作用对于指导组织特异性基因表达至关重要。为了构建这些组合的全局图谱，我们筛选了大多数人类和小鼠 DNA 结合转录因子（TF）之间的物理相互作用。完整的网络包含 762 个人类和 877 个小鼠相互作用。对网络的分析表明，高度连接的 TF 在组织中广泛表达，并且大约一半的测量相互作用在小鼠和人类之间是保守的。这些数据强调了 TF 组合对于确定细胞命运的重要性，并且导致了在免疫发育过程中表达的 SMAD3/FLI1 复合物的鉴定。人类和小鼠中大型 TF 组合网络的可用性将为研究基因调控、组织分化和哺乳动物进化提供许多机会。
