190 research outputs found
Functional definition of a transcription factor hierarchy regulating T cell lineage commitment
T cell factor 1 (Tcf1) is the first T cell-specific protein induced by Notch signaling in the thymus, leading to the activation of two major target genes, Gata3 and Bcl11b. Tcf1 deficiency results in partial arrests in T cell development, high apoptosis, and increased development of B and myeloid cells. Phenotypically, seemingly fully T cell-committed thymocytes with Tcf1 deficiency have promiscuous gene expression and an altered epigenetic profile and can dedifferentiate into more immature thymocytes and non-T cells. Restoring Bcl11b expression in Tcf1-deficient cells rescues T cell development but does not strongly suppress the development of non-T cells; in contrast, expressing Gata3 suppresses their development but does not rescue T cell development. Thus, T cell development is controlled by a minimal transcription factor network involving Notch signaling, Tcf1, and the subsequent division of labor between Bcl11b and Gata3, thereby ensuring a properly regulated T cell gene expression program.Molecular Technology and Informatics for Personalised Medicine and Healt
The role of MORC3 in silencing transposable elements in mouse embryonic stem cells
Background Microrchidia proteins (MORCs) are involved in epigenetic gene silencing in a variety of eukaryotic organisms. Deletion of MORCs result in several developmental abnormalities and their dysregulation has been implicated in developmental disease and multiple cancers. Specifically, mammalian MORC3 mutations are associated with immune system defects and human cancers such as bladder, uterine, stomach, lung, and diffuse large B cell lymphomas. While previous studies have shown that MORC3 binds to H3K4me3 in vitro and overlaps with H3K4me3 ChIP-seq peaks in mouse embryonic stem cells, the mechanism by which MORC3 regulates gene expression is unknown. Results In this study, we identified that mutation in Morc3 results in a suppressor of variegation phenotype in a Modifiers of murine metastable epialleles Dominant (MommeD) screen. We also find that MORC3 functions as an epigenetic silencer of transposable elements (TEs) in mouse embryonic stem cells (mESCs). Loss of Morc3 results in upregulation of TEs, specifically those belonging to the LTR class of retrotransposons also referred to as endogenous retroviruses (ERVs). Using ChIP-seq we found that MORC3, in addition to its known localization at H3K4me3 sites, also binds to ERVs, suggesting a direct role in regulating their expression. Previous studies have shown that these ERVs are marked by the repressive histone mark H3K9me3 which plays a key role in their silencing. However, we found that levels of H3K9me3 showed only minor losses in Morc3 mutant mES cells. Instead, we found that loss of Morc3 resulted in increased chromatin accessibility at ERVs as measured by ATAC-seq. Conclusions Our results reveal MORC3 as a novel regulator of ERV silencing in mouse embryonic stem cells. The relatively minor changes of H3K9me3 in the Morc3 mutant suggests that MORC3 acts mainly downstream of, or in a parallel pathway with, the TRIM28/SETDB1 complex that deposits H3K9me3 at these loci. The increased chromatin accessibility of ERVs in the Morc3 mutant suggests that MORC3 may act at the level of chromatin compaction to effect TE silencing.Molecular Technology and Informatics for Personalised Medicine and Healt
Study of the production of and hadrons in collisions and first measurement of the branching fraction
The product of the () differential production
cross-section and the branching fraction of the decay () is
measured as a function of the beauty hadron transverse momentum, ,
and rapidity, . The kinematic region of the measurements is and . The measurements use a data sample
corresponding to an integrated luminosity of collected by the
LHCb detector in collisions at centre-of-mass energies in 2011 and in 2012. Based on previous LHCb
results of the fragmentation fraction ratio, , the
branching fraction of the decay is
measured to be \begin{equation*} \mathcal{B}(\Lambda_b^0\rightarrow J/\psi
pK^-)= (3.17\pm0.04\pm0.07\pm0.34^{+0.45}_{-0.28})\times10^{-4},
\end{equation*} where the first uncertainty is statistical, the second is
systematic, the third is due to the uncertainty on the branching fraction of
the decay , and the
fourth is due to the knowledge of . The sum of the
asymmetries in the production and decay between and
is also measured as a function of and .
The previously published branching fraction of , relative to that of , is updated.
The branching fractions of are determined.Comment: 29 pages, 19figures. All figures and tables, along with any
supplementary material and additional information, are available at
https://lhcbproject.web.cern.ch/lhcbproject/Publications/LHCbProjectPublic/LHCb-PAPER-2015-032.htm
Measurements of long-range near-side angular correlations in TeV proton-lead collisions in the forward region
Two-particle angular correlations are studied in proton-lead collisions at a
nucleon-nucleon centre-of-mass energy of TeV, collected
with the LHCb detector at the LHC. The analysis is based on data recorded in
two beam configurations, in which either the direction of the proton or that of
the lead ion is analysed. The correlations are measured in the laboratory
system as a function of relative pseudorapidity, , and relative
azimuthal angle, , for events in different classes of event
activity and for different bins of particle transverse momentum. In
high-activity events a long-range correlation on the near side, , is observed in the pseudorapidity range . This
measurement of long-range correlations on the near side in proton-lead
collisions extends previous observations into the forward region up to
. The correlation increases with growing event activity and is found
to be more pronounced in the direction of the lead beam. However, the
correlation in the direction of the lead and proton beams are found to be
compatible when comparing events with similar absolute activity in the
direction analysed.Comment: All figures and tables, along with any supplementary material and
additional information, are available at
https://lhcbproject.web.cern.ch/lhcbproject/Publications/LHCbProjectPublic/LHCb-PAPER-2015-040.htm
Evidence for the strangeness-changing weak decay
Using a collision data sample corresponding to an integrated luminosity
of 3.0~fb, collected by the LHCb detector, we present the first search
for the strangeness-changing weak decay . No
hadron decay of this type has been seen before. A signal for this decay,
corresponding to a significance of 3.2 standard deviations, is reported. The
relative rate is measured to be
, where and
are the and fragmentation
fractions, and is the branching
fraction. Assuming is bounded between 0.1 and
0.3, the branching fraction would lie
in the range from to .Comment: 7 pages, 2 figures, All figures and tables, along with any
supplementary material and additional information, are available at
https://lhcbproject.web.cern.ch/lhcbproject/Publications/LHCbProjectPublic/LHCb-PAPER-2015-047.htm
flavour tagging using charm decays at the LHCb experiment
An algorithm is described for tagging the flavour content at production of
neutral mesons in the LHCb experiment. The algorithm exploits the
correlation of the flavour of a meson with the charge of a reconstructed
secondary charm hadron from the decay of the other hadron produced in the
proton-proton collision. Charm hadron candidates are identified in a number of
fully or partially reconstructed Cabibbo-favoured decay modes. The algorithm is
calibrated on the self-tagged decay modes and using of data collected by the LHCb
experiment at centre-of-mass energies of and
. Its tagging power on these samples of
decays is .Comment: All figures and tables, along with any supplementary material and
additional information, are available at
http://lhcbproject.web.cern.ch/lhcbproject/Publications/LHCbProjectPublic/LHCb-PAPER-2015-027.htm
First observation of the decay and a measurement of the ratio of branching fractions
The first observation of the decay using
data collected by the LHCb detector at a centre-of-mass energy of 7 TeV,
corresponding to an integrated luminosity of 36 pb, is reported. A
signal of events is obtained and the absence of signal is
rejected with a statistical significance of more than nine standard deviations.
The branching fraction is measured relative to
that of : , where the first uncertainty is statistical, the second systematic and
the third is due to the uncertainty on the ratio of the and
hadronisation fractions.Comment: 10 pages, 3 figures, submitted to Phys. Lett. B; ISSN 0370-269
Identification of beauty and charm quark jets at LHCb
Identification of jets originating from beauty and charm quarks is important
for measuring Standard Model processes and for searching for new physics. The
performance of algorithms developed to select - and -quark jets is
measured using data recorded by LHCb from proton-proton collisions at
TeV in 2011 and at TeV in 2012. The efficiency for
identifying a jet is about 65%(25%) with a probability for
misidentifying a light-parton jet of 0.3% for jets with transverse momentum
GeV and pseudorapidity . The dependence of
the performance on the and of the jet is also measured
Search for Bâșc decays to the ppâŸÏâș final state
A search for the decays of the B + c meson to pp-Ï + is performed for the first time using a data sample corresponding to an integrated luminosity of 3.0 fb -1 collected by the LHCb experiment in pp collisions at centre-of-mass energies of 7 and 8 TeV. No signal is found and an upper limit, at 95% confidence level, is set, fcfuĂB(B + c âppÏ + ) < 3.6Ă10-8 in the kinematic region m(pp) < 2.85 GeV/c2, p T (B) < 20 GeV/c and 2.0 < y(B) < 4.5, where B is the branching fraction and f c (f u ) is the fragmentation fraction of the b quark into a B c + (B + ) meson
Measurement of CP observables in B± â D(â)K± and B± â D(â)ϱ decays
Measurements of CP observables in B ± âD (â) K ± and B ± âD (â) Ï Â± decays are presented, where D (â) indicates a neutral D or D â meson that is an admixture of D (â)0 and DÂŻ (â)0 states. Decays of the D â meson to the DÏ 0 and DÎł final states are partially reconstructed without inclusion of the neutral pion or photon, resulting in distinctive shapes in the B candidate invariant mass distribution. Decays of the D meson are fully reconstructed in the K ± Ï â , K + K â and Ï + Ï â final states. The analysis uses a sample of charged B mesons produced in pp collisions collected by the LHCb experiment, corresponding to an integrated luminosity of 2.0, 1.0 and 2.0 fb â1 taken at centre-of-mass energies of s=7, 8 and 13 TeV, respectively. The study of B ± âD â K ± and B ± âD â Ï Â± decays using a partial reconstruction method is the first of its kind, while the measurement of B ± âDK ± and B ± âDÏ Â± decays is an update of previous LHCb measurements. The B ± âDK ± results are the most precise to date
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