219 research outputs found
CTIP2, une protéine multifonctionnelle : Implication en physiopathologie cellulaire et en thérapeutique
The transcription factor CTIP2 (BCL11B) is a multifunctional protein involved in numerous cell physiological processes. To date, many molecular mechanisms underlying this process have been discovered, which highlighted the importance of the epigenetic regulation of genes and the regulation of the elongation factor P-TEFb. Furthermore studies of the deregulation of CTIP2 showed the association of CTIP2 to numerous pathologies including cancer and cardiac hypertrophy. A better comprehension of the physiopathology of these diseases might lead to the design of therapeutical strategies intending to prevent CTIP2 deregulation. Moreover, CTIP2 and its associated proteins constitute potential targets in strategies aiming to reduce and/or purge HIV-1 cell reservoirs. English title : CTIP2, a multifunctional protein: cellular physiopathology and therapeutic implication
Epigenetic tethering of AID to the donor switch region during immunoglobulin class switch recombination
A complex of KAP1 and HP1 is needed to tether AID to the H3K9me3-marked donor switch region during CSR
Epigenetic regulation by RARα maintains ligand-independent transcriptional activity
Retinoic acid receptors (RARs) α, β and γ are key regulators of embryonic development. Hematopoietic differentiation is regulated by RARα, and several types of leukemia show aberrant RARα activity. Through microarray expression analysis, we identified transcripts differentially expressed between F9 wild-type (Wt) and RARα knockout cells cultured in the absence or presence of the RAR-specific ligand all trans retinoic acid (RA). We validated the decreased Mest, Tex13, Gab1, Bcl11a, Tcfap2a and HMGcs1 transcript levels, and increased Slc38a4, Stmn2, RpL39l, Ref2L, Mobp and Rlf1 transcript levels in the RARa knockout cells. The decreased Mest and Tex13 transcript levels were associated with increased promoter CpG-island methylation and increased repressive histone modifications (H3K9me3) in RARα knockout cells. Increased Slc38a4 and Stmn2 transcript levels were associated with decreased promoter CpG-island methylation and increased permissive histone modifications (H3K9/K14ac, H3K4me3) in RARα knockout cells. We demonstrated specific association of RARα and RXRα with the Mest promoter. Importantly, stable expression of a dominant negative, oncogenic PML–RARα fusion protein in F9 Wt cells recapitulated the decreased Mest transcript levels observed in RARα knockout cells. We propose that RARα plays an important role in cellular memory and imprinting by regulating the CpG methylation status of specific promoter regions
Achieving a cure for HIV infection: do we have reasons to be optimistic?
The introduction of highly active antiretroviral therapy (HAART) in 1996 has transformed a lethal disease to a chronic pathology with a dramatic decrease in mortality and morbidity of AIDS-related symptoms in infected patients. However, HAART has not allowed the cure of HIV infection, the main obstacle to HIV eradication being the existence of quiescent reservoirs. Several other problems have been encountered with HAART (such as side effects, adherence to medication, emergence of resistance and cost of treatment), and these motivate the search for new ways to treat these patients. Recent advances hold promise for the ultimate cure of HIV infection, which is the topic of this review. Besides these new strategies aiming to eliminate the virus, efforts must be made to improve current HAART. We believe that the cure of HIV infection will not be attained in the short term and that a strategy based on purging the reservoirs has to be associated with an aggressive HAART strategy
KRAB–Zinc Finger Proteins and KAP1 Can Mediate Long-Range Transcriptional Repression through Heterochromatin Spreading
Krüppel-associated box domain-zinc finger proteins (KRAB–ZFPs) are tetrapod-specific transcriptional repressors encoded in the hundreds by the human genome. In order to explore their as yet ill-defined impact on gene expression, we developed an ectopic repressor assay, allowing the study of KRAB–mediated transcriptional regulation at hundreds of different transcriptional units. By targeting a drug-controllable KRAB–containing repressor to gene-trapping lentiviral vectors, we demonstrate that KRAB and its corepressor KAP1 can silence promoters located several tens of kilobases (kb) away from their DNA binding sites, with an efficiency which is generally higher for promoters located within 15 kb or less. Silenced promoters exhibit a loss of histone H3-acetylation, an increase in H3 lysine 9 trimethylation (H3K9me3), and a drop in RNA Pol II recruitment, consistent with a block of transcriptional initiation following the establishment of silencing marks. Furthermore, we reveal that KRAB–mediated repression is established by the long-range spreading of H3K9me3 and heterochromatin protein 1 β (HP1β) between the repressor binding site and the promoter. We confirm the biological relevance of this phenomenon by documenting KAP1–dependent transcriptional repression at an endogenous KRAB–ZFP gene cluster, where KAP1 binds to the 3′ end of genes and mediates propagation of H3K9me3 and HP1β towards their 5′ end. Together, our data support a model in which KRAB/KAP1 recruitment induces long-range repression through the spread of heterochromatin. This finding not only suggests auto-regulatory mechanisms in the control of KRAB–ZFP gene clusters, but also provides important cues for interpreting future genome-wide DNA binding data of KRAB–ZFPs and KAP1
Gaia Data Release 3: The Galaxy in your preferred colours: Synthetic photometry from Gaia low-resolution spectra
Gaia Data Release 3 provides novel flux-calibrated low-resolution spectrophotometry for '220 million sources in the wavelength range 330 nm ≤ λ ≤ 1050 nm (XP spectra). Synthetic photometry directly tied to a flux in physical units can be obtained from these spectra for any passband fully enclosed in this wavelength range. We describe how synthetic photometry can be obtained from XP spectra, illustrating the performance that can be achieved under a range of different conditions - for example passband width and wavelength range - as well as the limits and the problems affecting it. Existing top-quality photometry can be reproduced within a few per cent over a wide range of magnitudes and colour, for wide and medium bands, and with up to millimag accuracy when synthetic photometry is standardised with respect to these external sources. Some examples of potential scientific application are presented, including the detection of multiple populations in globular clusters, the estimation of metallicity extended to the very metal-poor regime, and the classification of white dwarfs. A catalogue providing standardised photometry for 2.2×108sources in several wide bands of widely used photometric systems is provided (Gaia Synthetic Photometry Catalogue; GSPC) as well as a catalogue of '105 white dwarfs with DA/non-DA classification obtained with a Random Forest algorithm (Gaia Synthetic Photometry Catalogue for White Dwarfs; GSPC-WD)
Gaia Data Release 3: Exploring and mapping the diffuse interstellar band at 862 nm
Context. Diffuse interstellar bands (DIBs) are common interstellar absorption features in spectroscopic observations but their origins remain unclear. DIBs play an important role in the life cycle of the interstellar medium (ISM) and can also be used to trace Galactic structure. Aims. Here, we demonstrate the capacity of the Gaia-Radial Velocity Spectrometer (RVS) in Gaia DR3 to reveal the spatial distribution of the unknown molecular species responsible for the most prominent DIB at 862 nm in the RVS passband, exploring the Galactic ISM within a few kiloparsecs from the Sun. Methods. The DIBs are measured within the GSP-Spec module using a Gaussian profile fit for cool stars and a Gaussian process for hot stars. In addition to the equivalent widths and their uncertainties, Gaia DR3 provides their characteristic central wavelength, width, and quality flags. Results. We present an extensive sample of 476 117 individual DIB measurements obtained in a homogeneous way covering the entire sky. We compare spatial distributions of the DIB carrier with interstellar reddening and find evidence that DIB carriers are present in a local bubble around the Sun which contains nearly no dust. We characterised the DIB equivalent width with a local density of 0.19 ± 0.04 kpc1 and a scale height of 98.60 8.46+11.10 pc. The latter is smaller than the dust scale height, indicating that DIBs are more concentrated towards the Galactic plane. We determine the rest-frame wavelength with unprecedented precision (?0 = 8620.86 ± 0.019 in air) and reveal a remarkable correspondence between the DIB velocities and the CO gas velocities, suggesting that the 862 nm DIB carrier is related to macro-molecules. Conclusions. We demonstrate the unique capacity of Gaia to trace the spatial structure of the Galactic ISM using the 862 nm DIB
Gaia Focused Product Release: Radial velocity time series of long-period variables
Context: The third Gaia Data Release (DR3) provided photometric time series of more than 2 million long-period variable (LPV) candidates. Anticipating the publication of full radial-velocity data planned with Data Release 4, this Focused Product Release (FPR) provides radial-velocity time series for a selection of LPV candidates with high-quality observations.
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Aims: We describe the production and content of the Gaia catalog of LPV radial-velocity time series, and the methods used to compute the variability parameters published as part of the Gaia FPR.
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Methods: Starting from the DR3 catalog of LPV candidates, we applied several filters to construct a sample of sources with high-quality radial-velocity measurements. We modeled their radial-velocity and photometric time series to derive their periods and amplitudes, and further refined the sample by requiring compatibility between the radial-velocity period and at least one of the G, GBP, or GRP photometric periods.
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Results: The catalog includes radial-velocity time series and variability parameters for 9614 sources in the magnitude range 6 ≲ G/mag ≲ 14, including a flagged top-quality subsample of 6093 stars whose radial-velocity periods are fully compatible with the values derived from the G, GBP, and GRP photometric time series. The radial-velocity time series contain a mean of 24 measurements per source taken unevenly over a duration of about three years. We identify the great majority of the sources (88%) as genuine LPV candidates, with about half of them showing a pulsation period and the other half displaying a long secondary period. The remaining 12% of the catalog consists of candidate ellipsoidal binaries. Quality checks against radial velocities available in the literature show excellent agreement. We provide some illustrative examples and cautionary remarks.
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Conclusions: The publication of radial-velocity time series for almost ten thousand LPV candidates constitutes, by far, the largest such database available to date in the literature. The availability of simultaneous photometric measurements gives a unique added value to the Gaia catalog
Gaia Focused Product Release: Asteroid orbital solution: Properties and assessment
CONTEXT:
We report the exploitation of a sample of Solar System observations based on data from the third Gaia Data Release (Gaia DR3) of nearly 157 000 asteroids. It extends the epoch astrometric solution over the time coverage planned for the Gaia DR4, which is not expected before the end of 2025. This data set covers more than one full orbital period for the vast majority of these asteroids. The orbital solutions are derived from the Gaia data alone over a relatively short arc compared to the observation history of many of these asteroids.
AIMS:
The work aims to produce orbital elements for a large set of asteroids based on 66 months of accurate astrometry provided by Gaia and to assess the accuracy of these orbital solutions with a comparison to the best available orbits derived from independent observations. A second validation is performed with accurate occultation timings.
METHODS:
We processed the raw astrometric measurements of Gaia to obtain astrometric positions of moving objects with 1D sub-mas accuracy at the bright end. For each asteroid that we matched to the data, an orbit fitting was attempted in the form of the best fit of the initial conditions at the median epoch. The force model included Newtonian and relativistic accelerations to derive the observation equations, which were solved with a linear least-squares fit.
RESULTS:
Orbits are provided in the form of state vectors in the International Celestial Reference Frame for 156 764 asteroids, including near-Earth objects, main-belt asteroids, and Trojans. For the asteroids with the best observations, the (formal) relative uncertainty σa/a is better than 10-10. Results are compared to orbits available from the Jet Propulsion Laboratory and MPC. Their orbits are based on much longer data arcs, but from positions of lower quality. The relative differences in semi-major axes have a mean of 5 × 10-10 and a scatter of 5 × 10-
Gaia Early Data Release 3: The celestial reference frame (Gaia-CRF3)
CONTEXT:
Gaia-CRF3 is the celestial reference frame for positions and proper motions in the third release of data from the Gaia mission, Gaia DR3 (and for the early third release, Gaia EDR3, which contains identical astrometric results). The reference frame is defined by the positions and proper motions at epoch 2016.0 for a specific set of extragalactic sources in the (E)DR3 catalogue.
AIMS:
We describe the construction of Gaia-CRF3 and its properties in terms of the distributions in magnitude, colour, and astrometric quality.
METHODS:
Compact extragalactic sources in Gaia DR3 were identified by positional cross-matching with 17 external catalogues of quasi-stellar objects (QSO) and active galactic nuclei (AGN), followed by astrometric filtering designed to remove stellar contaminants. Selecting a clean sample was favoured over including a higher number of extragalactic sources. For the final sample, the random and systematic errors in the proper motions are analysed, as well as the radio-optical offsets in position for sources in the third realisation of the International Celestial Reference Frame (ICRF3).
RESULTS:
Gaia-CRF3 comprises about 1.6 million QSO-like sources, of which 1.2 million have five-parameter astrometric solutions in Gaia DR3 and 0.4 million have six-parameter solutions. The sources span the magnitude range G = 13–21 with a peak density at 20.6 mag, at which the typical positional uncertainty is about 1 mas. The proper motions show systematic errors on the level of 12 µas yr–1 on angular scales greater than 15 deg. For the 3142 optical counterparts of ICRF3 sources in the S/X frequency bands, the median offset from the radio positions is about 0.5 mas, but it exceeds 4 mas in either coordinate for 127 sources. We outline the future of Gaia-CRF in the next Gaia data releases. Appendices give further details on the external catalogues used, how to extract information about the Gaia-CRF3 sources, potential (Galactic) confusion sources, and the estimation of the spin and orientation of an astrometric solution
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