Kruppel-associated box zinc-finger proteins (KRAB-ZFPs) make up the largest family of transcription factors in humans. These proteins emerged in the last common ancestor of coelacanth and tetrapods, and have expanded and diversified in the mammalian lineage. Although their mechanism of transcriptional repression has been well studied for over a decade, the DNA-binding activities and the biological functions of these proteins have been largely unexplored. Recent large-scale ChIP-seq studies and loss-of-function experiments have revealed that KRAB-ZFPs play a major role in the recognition and transcriptional silencing of transposable elements (TEs), consistent with an ‘arms race model’ of KRAB-ZFP evolution against invading TEs. However, this model is insufficient to explain the evolution of many KRAB-ZFPs that appear to domesticate TEs for novel host functions. We highlight some of the mammalian regulatory innovations driven by specific KRAB-ZFPs, including genomic imprinting, meiotic recombination hotspot choice, and placental growth.

与Kruppel相关的盒锌指蛋白（KRAB-ZFP）构成了人类中最大的转录因子家族。这些蛋白质出现在腔棘鱼和四足动物的最后共同祖先中，并在哺乳动物谱系中扩展和多样化。尽管已经对其转录抑制机制进行了十多年的深入研究，但这些蛋白质的DNA结合活性和生物学功能尚未得到充分研究。最近的大规模ChIP-seq研究和功能丧失实验表明，KRAB-ZFP在转座因子（TE）的识别和转录沉默中起着重要作用，这与KRAB-ZFP的“军备竞赛模型”一致入侵TE的进化。然而，该模型不足以解释许多KRAB-ZFP的进化，这些进化似乎为新的宿主功能驯化了TE。我们重点介绍了由特定KRAB-ZFP驱动的一些哺乳动物监管创新，包括基因组印迹，减数分裂重组热点选择和胎盘生长。