13 research outputs found

    HDAC7 Is a Repressor of Myeloid Genes Whose Downregulation Is Required for Transdifferentiation of Pre-B Cells into Macrophages

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    B lymphopoiesis is the result of several cell-commitment, lineage-choice, and differentiation processes. Every differentiation step is characterized by the activation of a new, lineage-specific, genetic program and the extinction of the previous one. To date, the central role of specific transcription factors in positively regulating these distinct differentiation processes to acquire a B cell-specific genetic program is well established. However, the existence of specific transcriptional repressors responsible for the silencing of lineage inappropriate genes remains elusive. Here we addressed the molecular mechanism behind repression of non-lymphoid genes in B cells. We report that the histone deacetylase HDAC7 was highly expressed in pre-B cells but dramatically down-regulated during cellular lineage conversion to macrophages. Microarray analysis demonstrated that HDAC7 re-expression interfered with the acquisition of the gene transcriptional program characteristic of macrophages during cell transdifferentiation; the presence of HDAC7 blocked the induction of key genes for macrophage function, such as immune, inflammatory, and defense response, cellular response to infections, positive regulation of cytokines production, and phagocytosis. Moreover, re-introduction of HDAC7 suppressed crucial functions of macrophages, such as the ability to phagocytose bacteria and to respond to endotoxin by expressing major pro-inflammatory cytokines. To gain insight into the molecular mechanisms mediating HDAC7 repression in pre-B cells, we undertook co-immunoprecipitation and chromatin immunoprecipitation experimental approaches. We found that HDAC7 specifically interacted with the transcription factor MEF2C in pre-B cells and was recruited to MEF2 binding sites located at the promoters of genes critical for macrophage function. Thus, in B cells HDAC7 is a transcriptional repressor of undesirable genes. Our findings uncover a novel role for HDAC7 in maintaining the identity of a particular cell type by silencing lineage-inappropriate genes

    Observation of a mu s isomer in In-134(49)85: Proton-neutron coupling "southeast" of Sn-132(50)82

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    We report on the observation of a microsecond isomeric state in the single-proton-hole, three-neutron-particle nucleus ¹³⁴In. The nuclei of interest were produced by in-flight fission of a ²³⁸U beam at the Radioactive Isotope Beam Factory at RIKEN. The isomer depopulates through a γ ray of energy 56.7(1) keV and with a half-life of T1/2=3.5(4)μs. Based on the comparison with shell-model calculations, we interpret the isomer as the Iπ=5− member of the π0g−19/2⊗ν1f37/2 multiplet, decaying to the Iπ=7− ground state with a reduced-transition probability of B(E2;5−→7−)=0.53(6)W.u.Observation of this isomer, and lack of evidence in the current work for a Iπ=5− isomer decay in ¹³²In, provides a benchmark of the proton-neutron interaction in the region of the nuclear chart “southeast” of ¹³²Sn, where experimental information on excited states is sparse

    β-Delayed One and Two Neutron Emission Probabilities Southeast of ^{132}Sn and the Odd-Even Systematics in r-Process Nuclide Abundances.

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    The β-delayed one- and two-neutron emission probabilities (P_{1n} and P_{2n}) of 20 neutron-rich nuclei with N≥82 have been measured at the RIBF facility of the RIKEN Nishina Center. P_{1n} of ^{130,131}Ag, ^{133,134}Cd, ^{135,136}In, and ^{138,139}Sn were determined for the first time, and stringent upper limits were placed on P_{2n} for nearly all cases. β-delayed two-neutron emission (β2n) was unambiguously identified in ^{133}Cd and ^{135,136}In, and their P_{2n} were measured. Weak β2n was also detected from ^{137,138}Sn. Our results highlight the effect of the N=82 and Z=50 shell closures on β-delayed neutron emission probability and provide stringent benchmarks for newly developed macroscopic-microscopic and self-consistent global models with the inclusion of a statistical treatment of neutron and γ emission. The impact of our measurements on r-process nucleosynthesis was studied in a neutron star merger scenario. Our P_{1n} and P_{2n} have a direct impact on the odd-even staggering of the final abundance, improving the agreement between calculated and observed Solar System abundances. The odd isotope fraction of Ba in r-process-enhanced (r-II) stars is also better reproduced using our new data

    <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:mi>β</mml:mi></mml:math> -delayed neutron emissions from <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:mrow><mml:mi>N</mml:mi><mml:mo>&gt;</mml:mo><mml:mn>50</mml:mn></mml:mrow></mml:math> gallium isotopes

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    β-delayed γ-neutron spectroscopy has been performed on the decay of A=84 to 87 gallium isotopes at the RI-beam Factory at the RIKEN Nishina Center using a high-efficiency array of He3 neutron counters (BRIKEN). β-2n-γ events were measured in the decays of all of the four isotopes for the first time, which is direct evidence for populating the excited states of two-neutron daughter nuclei. Detailed decay schemes with the γ branching ratios were obtained for these isotopes, and the neutron emission probabilities (Pxn) were updated from the previous study. Hauser-Feshbach statistical model calculations were performed to understand the experimental branching ratios. We found that the P1n and P2n values are sensitive to the nuclear level densities of 1n daughter nuclei and showed that the statistical model reproduced the P2n/P1n ratio better when experimental levels plus shell-model level densities fit by the Gilbert-Cameron formula were used as the level-density input. We also showed the neutron and γ branching ratios are sensitive to the ground-state spin of the parent nucleus. Our statistical model analysis suggested J≤3 for the unknown ground-state spin of the odd-odd nucleus Ga86, from the Iγ(4+→2+)/Iγ(2+→0+) ratio of Ga84 and the P2n/P1n ratio. These results show the necessity of detailed understanding of the decay scheme, including data from neutron spectroscopy, in addition to γ measurements of the multineutron emitters
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