YihE Kinase Is a Central Regulator of Programmed Cell Death in Bacteria

赵西林教授长期从事抗生素作用机制与耐药、结核病新疗法、细菌应急应答等方向研究，于2012年底受聘为厦门大学公共卫生学院双聘教授，并作为课题组负责人筹建病原微生物与抗感染治疗课题组。Stress-mediated programmed cell death (PCD) in bacteria has recently attracted attention, largely because it raises novel possibilities for controlling pathogens. How PCD in bacteria is regulated to avoid population extinction due to transient, moderate stress remains a central question. Here, we report that the YihE protein kinase is a key regulator that protects Escherichia coli from antimicrobial and environmental stressors by antagonizing the MazEF toxin-antitoxin module. YihE was linked to a reactive oxygen species (ROS) cascade, and a deficiency of yihE stimulated stress-induced PCD even after stress dissipated. YihE was partially regulated by the Cpx envelope stress-response system, which, along with MazF toxin and superoxide, has both protective and destructive roles that help bacteria make a live-or-die decision in response to stress. YihE probably acts early in the stress response to limit self-sustaining ROS production and PCD. Inhibition of YihE may provide a way of enhancing antimicrobial lethality and attenuating virulence

Water vapor detection in the transmission spectra of HD 209458 b with the CARMENES NIR channel

Aims: We aim at detecting H$_2$O in the atmosphere of the hot Jupiter HD 209458 b and perform a multi-band study in the near infrared with CARMENES. Methods: The H$_2$O absorption lines from the planet's atmosphere are Doppler-shifted due to the large change in its radial velocity during transit. This shift is of the order of tens of km s$^{-1}$, whilst the Earth's telluric and the stellar lines can be considered quasi-static. We took advantage of this to remove the telluric and stellar lines using SYSREM, a principal component analysis algorithm. The residual spectra contain the signal from thousands of planetary molecular lines well below the noise level. We retrieve this information by cross-correlating the spectra with models of the atmospheric absorption. Results: We find evidence of H$_2$O in HD 209458 b with a signal-to-noise ratio (S/N) of 6.4. The signal is blueshifted by --5.2 $^{+2.6}_{-1.3}$ km s$^{-1}$, which, despite the error bars, is a firm indication of day-to-night winds at the terminator of this hot Jupiter. Additionally, we performed a multi-band study for the detection of H$_2$O individually from the three NIR bands covered by CARMENES. We detect H$_2$O from its 1.0 $\mu$m band with a S/N of 5.8, and also find hints from the 1.15 $\mu$m band, with a low S/N of 2.8. No clear planetary signal is found from the 1.4 $\mu$m band. Conclusions: Our significant signal from the 1.0 $\mu$m band in HD 209458 b represents the first detection of H$_2$O from this band, the bluest one to date. The unfavorable observational conditions might be the reason for the inconclusive detection from the stronger 1.15 and 1.4 $\mu$m bands. H$_2$O is detected from the 1.0 $\mu$m band in HD 209458 b, but hardly in HD 189733 b, which supports a stronger aerosol extinction in the latter.Comment: 11 pages, 10 figures; accepted for publication in A&

A giant exoplanet orbiting a very-low-mass star challenges planet formation models

Surveys have shown that super-Earth and Neptune-mass exoplanets are more frequent than gas giants around low-mass stars, as predicted by the core accretion theory of planet formation. We report the discovery of a giant planet around the very-low-mass star GJ 3512, as determined by optical and near-infrared radial-velocity observations. The planet has a minimum mass of 0.46 Jupiter masses, very high for such a small host star, and an eccentric 204-day orbit. Dynamical models show that the high eccentricity is most likely due to planet-planet interactions. We use simulations to demonstrate that the GJ 3512 planetary system challenges generally accepted formation theories, and that it puts constraints on the planet accretion and migration rates. Disk instabilities may be more efficient in forming planets than previously thought

CARMENES: high-resolution spectra and precise radial velocities in the red and infrared

SPIE Astronomical Telescopes + Instrumentation (2018, Austin, Texas, United States

Setd1a regulates progenitor B-cell-to-precursor B-cell development through histone H3 lysine 4 trimethylation and Ig heavy-chain rearrangement

SETD1A is a member of trithorax-related histone methyltransferases that methylate lysine 4 at histone H3 (H3K4). We showed previously that Setd1a is required for mesoderm specification and hematopoietic lineage differentiation in vitro. However, it remains unknown whether or not Setd1a controls specific hematopoietic lineage commitment and differentiation during animal development. Here, we reported that homozygous Setd1a knockout (KO) mice are embryonic lethal. Loss of the Setd1a gene in the hematopoietic compartment resulted in a blockage of the progenitor B-cell-to-precursor B-cell development in bone marrow (BM) and B-cell maturation in spleen. The Setd1a-cKO (conditional knockout) mice exhibited an enlarged spleen with disrupted spleen architecture and leukocytopenia. Mechanistically, Setd1a deficiency in BM reduced the levels of H3K4me3 at critical B-cell gene loci, including Pax5 and Rag1/2, which are critical for the IgH (Ig heavy-chain) locus contractions and rearrangement. Subsequently, the differential long-range looped interactions of the enhancer Eμ with proximal 5′ D(H) region and 3′ regulatory regions as well as with Pax5-activated intergenic repeat elements and 5′ distal V(H) genes were compromised by the Setd1a-cKO. Together, our findings revealed a critical role of Setd1a and its mediated epigenetic modifications in regulating the IgH rearrangement and B-cell development.—Tusi, B. K., Deng, C., Salz, T., Zeumer, L., Li, Y., So, C. W. E., Morel, L. M., Qiu, Y., Huang, S. Setd1a regulates progenitor B-cell-to-precursor B-cell development through histone H3 lysine 4 trimethylation and Ig heavy-chain rearrangement

USF1 and hSET1A Mediated Epigenetic Modifications Regulate Lineage Differentiation and <i>HoxB4</i> Transcription

<div><p>The interplay between polycomb and trithorax complexes has been implicated in embryonic stem cell (ESC) self-renewal and differentiation. It has been shown recently that WRD5 and Dpy-30, specific components of the SET1/MLL protein complexes, play important roles during ESC self-renewal and differentiation of neural lineages. However, not much is known about how and where specific trithorax complexes are targeted to genes involved in self-renewal or lineage-specification. Here, we report that the recruitment of the hSET1A histone H3K4 methyltransferase (HMT) complex by transcription factor USF1 is required for mesoderm specification and lineage differentiation. In undifferentiated ESCs, USF1 maintains hematopoietic stem/progenitor cell (HS/PC) associated bivalent chromatin domains and differentiation potential. Furthermore, USF1 directed recruitment of the hSET1A complex to the <i>HoxB4</i> promoter governs the transcriptional activation of <i>HoxB4</i> gene and regulates the formation of early hematopoietic cell populations. Disruption of USF or hSET1A function by overexpression of a dominant-negative AUSF1 mutant or by RNA-interference-mediated knockdown, respectively, led to reduced expression of mesoderm markers and inhibition of lineage differentiation. We show that USF1 and hSET1A together regulate H3K4me3 modifications and transcription preinitiation complex assembly at the hematopoietic-associated <i>HoxB4</i> gene during differentiation. Finally, ectopic expression of USF1 in ESCs promotes mesoderm differentiation and enforces the endothelial-to-hematopoietic transition by inducing hematopoietic-associated transcription factors, <i>HoxB4</i> and <i>TAL1</i>. Taken together, our findings reveal that the guided-recruitment of the hSET1A histone methyltransferase complex and its H3K4 methyltransferase activity by transcription regulator USF1 safeguards hematopoietic transcription programs and enhances mesoderm/hematopoietic differentiation.</p></div

ASH2L mediates USF1 interaction with the hSET1A core complex and <i>Hox</i> gene activation.

<p>(A) Schematic representation of the <i>HoxB4</i> promoter driven pREP4 luciferase episomal reporter construct. (B) K562 cells were transfected with a pREP4-hHoxB4-luc reporter, an expression vector for USF1, and siRNA targeting hSET1A, HCF1, ASH2L or PRMT1. A CMV-driven renilla luciferase plasmid was used as a transfection control. Transfected cells were cultured for 48 hrs and lysed for measurement of luciferase activity. Data are shown as mean ± SD. ** P<0.01; * P<0.05. (C) Western blotting analysis of the levels of ASH2L, hEST1A, PRMT1, and α-tubulin in K562 cells transfected with luciferase reporter and siRNA constructs. (D) ChIP analysis of USF1 binding, HCF1 recruitment, and H3K4me3 association in K562 cells transfected with the pREP4-hHoxB4-luc reporter, an expression vector for USF1, siControl, or siRNA targeting hSET1A. Data are shown as mean ± SD. ** P<0.01. (E)ASH2L of the hSET1A core complex directly interacts with GST-USF1. GST-USF1, pre-absorbed to glutathione-sepharose beads, was incubated with each Flag tagged component of the hSET1A complex and analyzed by WB with Flag antibody (Top). Expression of the hSET1A components purified from virally infected SF9 cells (Bottom). (F)Co-IP assay in K562 cells showing USF1 associates with hSET1A but not with MLL1. (G) Co-IP assay in K562 cells showing that the USF1 associated hSET1A complex does not contain CFP1. (H) Interaction of USF1 with hSET1A in the presence but not absence of ASH2L. GST-USF1 was pre-absorbed to glutathione-sepharose beads and incubated with the purified, baculovirus reconstituted hSET1A complex with or without ASH2L (Top). Immunoblots of the purified, baculovirus expressing hSET1A complex components with or without ASH2L are shown as inputs (Bottom).</p