Inflammatory ILC2s are itinerant sentinels: Group 2 innate lymphoid cells (ILC2s) are a population of immune cells that play important roles in tissue homeostasis and barrier immunity to helminths. Recent work has suggested that ILC2s are primarily long-term residents of tissues that do not readily recirculate. Huanget al.now demonstrate, however, that these findings do not necessarily hold true for the interleukin-25 (IL-25)–responsive KLRG1^hi“inflammatory” ILC2 (iILC2) subset (see the Perspective by Mjösberg and Rao). In response to exogenous IL-25 or helminth infection, iILC2 precursors in the small intestinal lamina propria proliferate and alter their expression of sphingosine 1-phosphate (S1P) receptors. They then traffic to both lymphatic and nonlymphatic organs in a partly S1P-dependent manner, participating in vital anti-helminth and tissue repair responses.Science, this issue p.114; see also p.36

Life experience can leave lasting marks, such as epigenetic changes, in the brain. How life experience is translated into storable epigenetic information remains largely unknown. With unbiased data-driven approaches, we predicted that Egr1, a transcription factor important for memory formation, plays an essential role in brain epigenetic programming. We performed EGR1 ChIP-seq and validated thousands of EGR1 binding sites with methylation patterns established during postnatal brain development. More specifically, these EGR1 binding sites become hypomethylated in mature neurons but remain heavily methylated in glia. We further demonstrated that EGR1 recruits a DNA demethylase TET1 to remove the methylation marks and activate downstream genes. The frontal cortices from the knockout mice lacking Egr1 or Tet1 share strikingly similar profiles in both gene expression and DNA methylation. In summary, our study reveals EGR1 programs the brain methylome together with TET1 providing new insight into how life experience may shape the brain methylome.

Motivation: Bacterial type III secreted (T3S) effectors are delivered into host cells specifically via type III secretion systems (T3SSs), which play important roles in the interaction between bacteria and their hosts. Previous computational methods for T3S protein prediction have only achieved limited accuracy, and distinct features for effective T3S protein prediction remain to be identified. Results: In this work, a distinctive N-terminal position-specific amino acid composition (Aac) feature was identified for T3S proteins. A large portion (∼50%) of T3S proteins exhibit distinct position-specific Aac features that can tolerate position shift. A classifier, BPBAac, was developed and trained using Support Vector Machine (SVM) based on the Aac feature extracted using a Bi-profile Bayes model. We demonstrated that the BPBAac model outperformed other implementations in classification of T3S and non-T3S proteins, giving an average sensitivity of ∼90.97% and an average selectivity of ∼97.42% in a 5-fold cross-validation evaluation. The model was also robust when a small-size training dataset was used. The fact that the position-specific Aac feature is commonly found in T3S proteins across different bacterial species gives this model wide application. To demonstrate the model's application, a genome-wide prediction of T3S effector proteins was performed for Ralstonia solanacearum, an important plant pathogenic bacterium, and a number of putative candidates were identified using this model. Availability: An R package of BPBAac tool is freely downloadable from: http://biocomputer.bio.cuhk.edu.hk/softwares/BPBAac. Contact:djguo@cuhk.edu.hk Supplementary information: Supplementary data are available at Bioinformatics online.

The faithful transmission of DNA methylation patterns through cell divisions is essential for the daughter cells to retain a proper cell identity. To achieve a comprehensive assessment of methylation fidelity, we implemented a genome-scale hairpin bisulfite sequencing approach to generate methylation data for DNA double strands simultaneously. We show here that methylation fidelity increases globally during differentiation of mouse embryonic stem cells (mESCs), and is particularly high in the promoter regions of actively expressed genes and positively correlated with active histone modification marks and binding of transcription factors. The majority of intermediately (40%–60%) methylated CpG dinucleotides are hemi-methylated and have low methylation fidelity, particularly in the differentiating mESCs. While 5-hmC and 5-mC tend to coexist, there is no significant correlation between 5-hmC levels and methylation fidelity. Our findings may shed new light on our understanding of the origins of methylation variations and the mechanisms underlying DNA methylation transmission.

Pregnancy and parturition are intricately regulated to ensure successful reproductive outcomes. However, the factors that control gestational length in humans and other anthropoid primates remain poorly defined. Here, we show the endogenous retroviral long terminal repeat transposon-like human element 1B (THE1B) selectively controls placental expression of corticotropin-releasing hormone (CRH) that, in turn, influences gestational length and birth timing. Placental expression of CRH and subsequently prolonged gestational length were found in two independent strains of transgenic mice carrying a 180-kb human bacterial artificial chromosome (BAC) DNA that contained the full length of CRH and extended flanking regions, including THE1B. Restricted deletion of THE1B silenced placental CRH expression and normalized birth timing in these transgenic lines. Furthermore, we revealed an interaction at the 5′ insertion site of THE1B with distal-less homeobox 3 (DLX3), a transcription factor expressed in placenta. Together, these findings suggest that retroviral insertion of THE1B into the anthropoid primate genome may have initiated expression of CRH in placental syncytiotrophoblasts via DLX3 and that this placental CRH is sufficient to alter the timing of birth. The proper timing of delivery is critical during pregnancy; if too early or too late, the baby will be at risk of serious health problems and even death. Corticotropin-releasing hormone (CRH) is a protein that can be detected in maternal blood, and its concentration correlates with the timing of birth. In humans and other anthropoid primates, CRH is made by the placenta, whereas in other mammals, it is produced in a specialized region of the brain. To understand the regulation and evolution of this key protein, we inserted the human CRH gene and nearby regions into the mouse genome, which resulted in human CRH expression in the mouse placenta. Mouse litters that make CRH in their placentas are born later than control mice, showing that CRH can directly affect birth timing. Using our mouse model, we then selectively deleted a remnant of an ancient retrovirus that is normally found in the DNA of anthropoid primates and demonstrated that this specific region controls expression of CRH in the placenta. Deletion of this region also restored normal birth timing in the mice by eliminating CRH production from the placenta. We propose that retroviral regulation of CRH in the placenta may be a mechanism of controlling birth timing in humans and other anthropoid primates.