H2A.Z facilitates licensing and activation of early replication origins.

DNA replication is a tightly regulated process that ensures the precise duplication of the genome during the cell cycle1. In eukaryotes, the licensing and activation of replication origins are regulated by both DNA sequence and chromatin features2. However, the chromatin-based regulatory mechanisms remain largely uncharacterized. Here we show that, in HeLa cells, nucleosomes containing the histone variant H2A.Z are enriched with histone H4 that is dimethylated on its lysine 20 residue (H4K20me2) and with bound origin-recognition complex (ORC). In vitro studies show that H2A.Z-containing nucleosomes bind directly to the histone lysine methyltransferase enzyme SUV420H1, promoting H4K20me2 deposition, which is in turn required for ORC1 binding. Genome-wide studies show that signals from H4K20me2, ORC1 and nascent DNA strands co-localize with H2A.Z, and that depletion of H2A.Z results in decreased H4K20me2, ORC1 and nascent-strand signals throughout the genome. H2A.Z-regulated replication origins have a higher firing efficiency and early replication timing compared with other origins. Our results suggest that the histone variant H2A.Z epigenetically regulates the licensing and activation of early replication origins and maintains replication timing through the SUV420H1-H4K20me2-ORC1 axis.

Author Correction: H2A.Z facilitates licensing and activation of early replication origins.

An Amendment to this paper has been published and can be accessed via a link at the top of the paper.

Unveiling the unique role of iron in the metabolism of methanogens: A review.

Methanogens are the main participants in the carbon cycle, catalyzing five methanogenic pathways. Methanogens utilize different iron-containing functional enzymes in different methanogenic processes. Iron is a vital element in methanogens, which can serve as a carrier or reactant in electron transfer. Therefore, iron plays an important role in the growth and metabolism of methanogens. In this paper, we cast light on the types and functions of iron-containing functional enzymes involved in different methanogenic pathways, and the roles iron play in energy/substance metabolism of methanogenesis. Furthermore, this review provides certain guiding significance for lowering CH4 emissions, boosting the carbon sink capacity of ecosystems and promoting green and low-carbon development in the future.

Type 3 Innate Lymphoid Cells Direct Goblet Cell Differentiation via the LT-LTßR Pathway during Listeria Infection.

As a specialized subset of intestinal epithelial cells (IECs), goblet cells (GCs) play an important role during the antibacterial response via mucin production. However, the regulatory mechanisms involved in GC differentiation and function during infection, particularly the role of immune cell-IEC cross-talk, remain largely unknown. In this study, using Villin∆Ltbr conditional knockout mice, we demonstrate that LTßR, expressed on IECs, is required for GC hyperplasia and mucin 2 (MUC2) expression during Listeria infection for host defense but not homeostatic maintenance in the naive state. Analysis of single gene-deficient mice revealed that the ligand lymphotoxin (LT), but not LIGHT, and type 3 innate lymphoid cells (ILC3s), but not conventional T cells, are required for MUC2-dependent Listeria control. Conditional deficiency of LT in ILC3s further confirmed the importance of LT signals derived from ILC3s. Lack of ILC3-derived LT or IEC-derived LTßR resulted in the defective expression of genes related to GC differentiation but was not correlated with IEC proliferation and cell death, which were found to be normal by Ki-67 and Annexin V staining. In addition, the alternative NF-κB signaling pathway (involving RelB) in IECs was found to be required for the expression of GC differentiation-related genes and Muc2 and required for the anti-Listeria response. Therefore, our data together suggest a previously unrecognized ILC3-IEC interaction and LT-LTßR-RelB signaling axis governing GC differentiation and function during Listeria infection for host defense.

Measuring the phase noise of Raman lasers with an atom-based method.

Phase noise of Raman lasers is a major source of noise for a Raman-type cold atom interferometer, which is traditionally measured using the signal source analyzer. We report here an atom-based method to measure the phase noise performance between two Raman lasers. By analyzing and calibrating the system noise sources, we can characterize the contribution of phase noise from the total deviation of the relative atom population at the middle of the interference fringe. Knowing the transfer function specified by the operation sequence of the interferometer, we can obtain the transfer function and power spectrum density of the phase noise term. By varying the time sequences of the interferometer, we can measure the white phase noise floor and the phase noise performance over a large range of Fourier frequencies from 1 to 100 000 Hz with a minor difference of 1 dB compared with results from the traditional method using a signal analyzer, which proves the validity of the atom-based method. Compared with the traditional measurement method, the atom-based method can have higher accuracy and have the ability of self-calibrating.

A new method for high-bandwidth servo control of the power ratio between two Raman beams for cold atom interferometer.

Light shift produced by the AC Stark effect is one of the major factors limiting the accuracy and long-term stability of a cold atom interferometer. The first order light shift can be canceled by fixing the power ratio of the Raman beams at a specified value. We report here a new method to stabilize the power ratio of the two Raman lasers with ∼100 kHz locking bandwidth, suppressing the effect of the first order light shift. We first mixed the two Raman lasers (at different optical frequencies) with a reference beam and then used two Schottky diode detectors to extract the corresponding beat note signals for each beam, which are much easier to be manipulated and processed as they are in the microwave band. The stability of the power ratio is improved by three orders of magnitude from 5.84 × 10-3 to 3.51 × 10-6 at 1 s averaging time and reaches 1.59 × 10-7 at 10 000 s integrating time when the servo loop is engaged. This method can be used in other precise quantum measurement based on the stimulated Raman transition and can be applied to compact inertial sensors.

LTßR controls thymic portal endothelial cells for haematopoietic progenitor cell homing and T-cell regeneration.

Continuous thymic homing of haematopoietic progenitor cells (HPCs) via the blood is critical for normal T-cell development. However, the nature and the differentiation programme of specialized thymic endothelial cells (ECs) controlling this process remain poorly understood. Here using conditional gene-deficient mice, we find that lymphotoxin beta receptor (LTßR) directly controls thymic ECs to guide HPC homing. Interestingly, T-cell deficiency or conditional ablation of T-cell-engaged LTßR signalling results in a defect in thymic HPC homing, suggesting the feedback regulation of thymic progenitor homing by thymic products. Furthermore, we identify and characterize a special thymic portal EC population with features that guide HPC homing. LTßR is essential for the differentiation and homeostasis of these thymic portal ECs. Finally, we show that LTßR is required for T-cell regeneration on irradiation-induced thymic injury. Together, these results uncover a cellular and molecular pathway that governs thymic EC differentiation for HPC homing.

Herpes virus entry mediator licenses Listeria infection induced immunopathology through control of type I interferon.

Apoptosis of the splenic lymphocytes is often induced during the acute phase of Listeria infection in mice. However, the underlying mechanism remains incompletely understood. Here, we found that herpes virus entry mediator (HVEM) plays an important role for Listeria infection induced lymphocyte apoptosis. Mechanistically, HVEM is not directly involved in listeriolysin O (LLO) induced lymphocyte apoptosis or interferon beta induced T cell activation per se. Interestingly, HVEM is partially required for Listeria induced interferon (IFN)-I production in the spleen, particularly in macrophages. Consequently, the bystander activation of lymphocytes is significantly lower in HVEM deficient mice than that in wild-type (WT) mice upon Listeria infection. Thus, our results have revealed a novel role of HVEM on the regulation of IFN-I and immunopathology during Listeria infection.