Characterization of Transcription from TATA-Less Promoters: Identification of a New Core Promoter Element XCPE2 and Analysis of Factor Requirements

More than 80% of mammalian protein-coding genes are driven by TATA-less promoters which often show multiple transcriptional start sites (TSSs). However, little is known about the core promoter DNA sequences or mechanisms of transcriptional initiation for this class of promoters.Here we identify a new core promoter element XCPE2 (X core promoter element 2) (consensus sequence: A/C/G-C-C/T-C-G/A-T-T-G/A-C-C/A(+1)-C/T) that can direct specific transcription from the second TSS of hepatitis B virus X gene mRNA. XCPE2 sequences can also be found in human promoter regions and typically appear to drive one of the start sites within multiple TSS-containing TATA-less promoters. To gain insight into mechanisms of transcriptional initiation from this class of promoters, we examined requirements of several general transcription factors by in vitro transcription experiments using immunodepleted nuclear extracts and purified factors. Our results show that XCPE2-driven transcription uses at least TFIIB, either TFIID or free TBP, RNA polymerase II (RNA pol II) and the MED26-containing mediator complex but not Gcn5. Therefore, XCPE2-driven transcription can be carried out by a mechanism which differs from previously described TAF-dependent mechanisms for initiator (Inr)- or downstream promoter element (DPE)-containing promoters, the TBP- and SAGA (Spt-Ada-Gcn5-acetyltransferase)-dependent mechanism for yeast TATA-containing promoters, or the TFTC (TBP-free-TAF-containing complex)-dependent mechanism for certain Inr-containing TATA-less promoters. EMSA assays using XCPE2 promoter and purified factors further suggest that XCPE2 promoter recognition requires a set of factors different from those for TATA box, Inr, or DPE promoter recognition.We identified a new core promoter element XCPE2 that are found in multiple TSS-containing TATA-less promoters. Mechanisms of promoter recognition and transcriptional initiation for XCPE2-driven promoters appear different from previously shown mechanisms for classical promoters that show single "focused" TSSs. Our studies provide insight into novel mechanisms of RNA Pol II transcription from multiple TSS-containing TATA-less promoters

Insights into the Molecular Mechanisms of the Anti-Atherogenic Actions of Flavonoids in Normal and Obese Mice

Obesity is a major and independent risk factor for cardiovascular disease and it is strongly associated with the development of dyslipidemia, insulin resistance and type 2 diabetes. Flavonoids, a diverse group of polyphenol compounds of plant origin widely distributed in human diet, have been reported to have numerous health benefits, although the mechanisms underlying these effects have remained obscure. We analyzed the effects of chronic dietary supplementation with flavonoids extracted from cranberry (FLS) in normal and obese C57/BL6 mice compared to mice maintained on the same diets lacking FLS. Obese mice supplemented with flavonoids showed an amelioration of insulin resistance and plasma lipid profile, and a reduction of visceral fat mass. We provide evidence that the adiponectin-AMPK pathway is the main mediator of the improvement of these metabolic disorders. In contrast, the reduced plasma atherogenic cholesterol observed in normal mice under FLS seems to be due to a downregulation of the hepatic cholesterol synthesis pathway. Overall, we demonstrate for the first time that the molecular mechanisms underlying the beneficial effects of flavonoids are determined by the metabolic state

The Imaging X-ray Polarimetry Explorer (IXPE) at last!

IXPE, the first observatory dedicated to imaging X-ray polarimetry, was launched on Dec 9, 2021 and is operating successfully. A partnership between NASA and the Italian Space Agencey (ASI) IXPE features three X-ray telescopes each comprised of a mirror module assembly with a polarization sensitive detector at its focus. An extending boom was deployed on orbit to provide the necessary 4 m focal length. A 3-axis-stabilized spacecraft provides power, attitude determination and control, and commanding. After one year of observation IXPE has measured statistically-significant polarization from almost all the classes of celestial sources that emit X-rays. In the following we describe the IXPE mission, reporting on its performance after 1.5 year of operations. We show the main astrophysical results which are outstanding for a SMEX mission

Complex variations in X-ray polarization in the X-ray pulsar LS V +44 17/RX J0440.9+4431

We report on Imaging X-ray polarimetry explorer (IXPE) observations of the Be-transient X-ray pulsar LS V +44 17/RX J0440.9+4431 made at two luminosity levels during the giant outburst in January- February 2023. Considering the observed spectral variability and changes in the pulse profiles, the source was likely caught in supercritical and subcritical states with significantly different emission-region geometry, associated with the presence of accretion columns and hot spots, respectively. We focus here on the pulse-phase-resolved polarimetric analysis and find that the observed dependencies of the polarization degree and polarization angle (PA) on the pulse phase are indeed drastically different for the two observations. The observed differences, if interpreted within the framework of the rotating vector model (RVM), imply dramatic variations in the spin axis inclination, the position angle, and the magnetic colatitude by tens of degrees within the space of just a few days. We suggest that the apparent changes in the observed PA phase dependence are predominantly related to the presence of an unpulsed polarized component in addition to the polarized radiation associated with the pulsar itself. We then show that the observed PA phase dependence in both observations can be explained with a single set of RVM parameters defining the pulsar s geometry. We also suggest that the additional polarized component is likely produced by scattering of the pulsar radiation in the equatorial disk wind

The Polarized Cosmic Hand: IXPE Observations of PSR B1509−58/MSH 15−52

We describe IXPE polarization observations of the pulsar wind nebula (PWN) MSH 15−52, the “Cosmic Hand.” We find X-ray polarization across the PWN, with B-field vectors generally aligned with filamentary X-ray structures. High-significance polarization is seen in arcs surrounding the pulsar and toward the end of the “jet,” with polarization degree PD > 70%, thus approaching the maximum allowed synchrotron value. In contrast, the base of the jet has lower polarization, indicating a complex magnetic field at significant angle to the jet axis. We also detect significant polarization from PSR B1509−58 itself. Although only the central pulse phase bin of the pulse has high individual significance, flanking bins provide lower-significance detections and, in conjunction with the X-ray image and radio polarization, can be used to constrain rotating vector model solutions for the pulsar geometry

A polarimetrically oriented X-ray stare at the accreting pulsar EXO 2030+375

Accreting X-ray pulsars (XRPs) are presumed to be ideal targets for polarization measurements, as their high magnetic field strength is expected to polarize the emission up to a polarization degree of 80%. However, such expectations are being challenged by recent observations of XRPs with the Imaging X-ray Polarimeter Explorer (IXPE). Here, we report on the results of yet another XRP, namely, EXO 2030+375, observed with IXPE and contemporarily monitored with Insight-HXMT and SRG/ART-XC. In line with recent results obtained with IXPE for similar sources, an analysis of the EXO 2030+375 data returns a low polarization degree of 0%- 3% in the phase-averaged study and a variation in the range of 2%- 7% in the phase-resolved study. Using the rotating vector model, we constrained the geometry of the system and obtained a value of 60 for the magnetic obliquity. When considering the estimated pulsar inclination of 130, this also indicates that the magnetic axis swings close to the observera's line of sight. Our joint polarimetric, spectral, and timing analyses hint toward a complex accreting geometry, whereby magnetic multipoles with an asymmetric topology and gravitational light bending significantly affect the behavior of the observed source

Discovery of X-Ray Polarization from the Black Hole Transient Swift J1727.8−1613

We report the first detection of the X-ray polarization of the bright transient Swift J1727.8−1613 with the Imaging X-ray Polarimetry Explorer. The observation was performed at the beginning of the 2023 discovery outburst, when the source resided in the bright hard state. We find a time- and energy-averaged polarization degree of 4.1% ± 0.2% and a polarization angle of 2.°2 ± 1.°3 (errors at 68% confidence level; this translates to ∼20σ significance of the polarization detection). This finding suggests that the hot corona emitting the bulk of the detected X-rays is elongated, rather than spherical. The X-ray polarization angle is consistent with that found in submillimeter wavelengths. Since the submillimeter polarization was found to be aligned with the jet direction in other X-ray binaries, this indicates that the corona is elongated orthogonal to the jet

Highly Significant Detection of X-Ray Polarization from the Brightest Accreting Neutron Star Sco X-1

The Imaging X-ray Polarimetry Explorer measured with high significance the X-ray polarization of the brightest Z-source, Sco X-1, resulting in the nominal 2–8 keV energy band in a polarization degree of 1.0% ± 0.2% and a polarization angle of 8° ± 6° at a 90% confidence level. This observation was strictly simultaneous with observations performed by NICER, NuSTAR, and Insight-HXMT, which allowed for a precise characterization of its broadband spectrum from soft to hard X-rays. The source has been observed mainly in its soft state, with short periods of flaring. We also observed low-frequency quasiperiodic oscillations. From a spectropolarimetric analysis, we associate a polarization to the accretion disk at <3.2% at 90% confidence level, compatible with expectations for an electron scattering dominated optically thick atmosphere at the Sco X-1 inclination of ∼44°; for the higher-energy Comptonized component, we obtain a polarization of 1.3% ± 0.4%, in agreement with expectations for a slab of Thomson optical depth of ∼7 and an electron temperature of ∼3 keV. A polarization rotation with respect to previous observations by OSO-8 and PolarLight, and also with respect to the radio-jet position angle, is observed. This result may indicate a variation of the polarization with the source state that can be related to relativistic precession or a change in the corona geometry with the accretion flow

X-ray polarimetry of the accreting pulsar GX 301-2

The phase- and energy-resolved polarization measurements of accreting X-ray pulsars (XRPs) allow us to test different theoretical models of their emission, and they also provide an avenue to determine the emission region geometry. We present the results of the observations of the XRP GX 301-2 performed with the Imaging X-ray Polarimetry Explorer (IXPE). A persistent XRP, GX 301-2 has one of the longest spin periods known: ∼680 s. A massive hyper-giant companion star Wray 977 supplies mass to the neutron star via powerful stellar winds. We did not detect significant polarization in the phase-averaged data when using spectro-polarimetric analysis, with the upper limit on the polarization degree (PD) of 2.3% (99% confidence level). Using the phase-resolved spectro-polarimetric analysis, we obtained a significant detection of polarization (above 99% confidence level) in two out of nine phase bins and a marginal detection in three bins, with a PD ranging between ∼3% and ∼10% and a polarization angle varying in a very wide range from ∼0 to ∼160. Using the rotating vector model, we obtained constraints on the pulsar geometry using both phase-binned and unbinned analyses, finding excellent agreement. Finally, we discuss possible reasons for a low observed polarization in GX 301-2