The Krüppel-associated box zinc finger protein (KRAB-ZFP) family diversified in mammals. The majority of human KRAB-ZFPs bind transposable elements (TEs), however, since most TEs are inactive in humans it is unclear whether KRAB-ZFPs emerged to suppress TEs. We demonstrate that many recently emerged murine KRAB-ZFPs also bind to TEs, including the active ETn, IAP, and L1 families. Using a CRISPR/Cas9-based engineering approach, we genetically deleted five large clusters of KRAB-ZFPs and demonstrate that target TEs are de-repressed, unleashing TE-encoded enhancers. Homozygous knockout mice lacking one of two KRAB-ZFP gene clusters on chromosome 2 and chromosome 4 were nonetheless viable. In pedigrees of chromosome 4 cluster KRAB-ZFP mutants, we identified numerous novel ETn insertions with a modest increase in mutants. Our data strongly support the current model that recent waves of retrotransposon activity drove the expansion of KRAB-ZFP genes in mice and that many KRAB-ZFPs play a redundant role restricting TE activity.

The concept of dynamic heterogeneity and the picture of the supercooled liquid as a mosaic of environments with distinct dynamics that interchange in time have been invoked to explain the nonexponential relaxations measured in these systems. The spatial extent and temporal persistence of these regions of distinct dynamics have remained challenging to identify. Here, singlemolecule fluorescence measurements using a probe similar in size and mobility to the host o-terphenyl unambiguously reveal exponential relaxations distributed in time and space and directly demonstrate ergodicity of the system down to the glass transition temperature. In the temperature range probed, at least 200 times the structural relaxation time of the host is required to recover ensemble-averaged relaxation at every spatial region in the system.espite decades of intensive study, a full theory of the glass transition is lacking; so too is a full understanding of the causal relationships between the unusual phenomena displayed by glass-forming liquids in the supercooled regime and the glass transition. One such phenomenon is the onset of nonexponential relaxations in the supercooled regime. Consistent with such relaxations, a variety of experiments have suggested the presence of dynamic heterogeneity, where-over a given time-molecular mobility in a given region may differ by orders of magnitude from that in another region, potentially just nanometers away (1, 2). While some experiments have sought to quantify the size of these regions, others have sought to quantify their persistence in time, as supercooled liquids are assumed to be ergodic, requiring that over long times, all dynamic environments are sampled (3-5). Precise description of dynamic heterogeneity in glass formers remains challenging due to the ensemble, subensemble, and/or time averaging inherent in most experimental techniques. However, such description remains of significant interest given the poorly understood causal relationship between dynamic heterogeneity and the glass transition as well as the need for experimental observations that may distinguish between various theories of the glass transition (6, 7).Typically, putative dynamic heterogeneity has been recognized in experiments through the shape of the ensemble relaxation, which is well described by a stretched exponential (exp[−(t/τ fit ) β ]) where the deviation of β below 1 describes the degree of stretching and has been interpreted as a barometer of dynamic heterogeneity. Multiple scenarios are consistent with an ensemble stretched exponential relaxation, and two limiting cases can be straightforwardly described: The ensemble stretched exponential emerges from (i) a superposition of exponentials with different relaxation times or (ii) identical stretched exponentials with the same relaxation time. The former limit describes a system with variation of time scales distributed in space but not time, while the latter represents the opposite extreme. The former case describes a system that is not ergodic over times acce...

Insulin-like growth factor 2 (IGF2) is the major fetal growth hormone in mammals. We identify zinc finger protein 568 (ZFP568), a member of the rapidly evolving Kruppel-associated box-zinc finger protein (KRAB-ZFP) family linked primarily to silencing of endogenous retroelements, as a direct repressor of a placental-specific transcript (designated) in mice. Loss of , which causes gastrulation failure, or mutation of the ZFP568-binding site at the promoter causes inappropriate activation. Deletion of can completely rescue gastrulation phenotypes through late gestation. Our data highlight the exquisite selectivity with which members of the KRAB-ZFP family repress their targets and identify an additional layer of transcriptional control of a key growth factor regulating fetal and placental development.