M Busslinger

..This suggests that Xist function is restricted in development by the limited activity of epigenetic pathways rather than by a change in the responsiveness of chromatin between embryonic and differentiated cell types...

..Hence, Pax5 expression is continuously required to maintain B cell lineage commitment, because its loss converts committed pro-B cells into hematopoietic progenitors with multilineage potential...

..Finally, IRF4 and IRF8 together control the termination of pre-B cell receptor signaling and thus promote differentiation to small pre-B cells undergoing light-chain gene rearrangements...

..In contrast, loss- and gain-of-function analyses have implicated the Notch1 receptor in the specification of the T cell fate, which may thus be controlled by instructive signals in the thymus...

..Together these data demonstrate that the transcription factors Pax2 and Pax5 have maintained equivalent biochemical functions since their divergence early in vertebrate evolution...

..Similar allele-specific regulation may be a common mechanism causing the haploinsufficiency and frequent association of other Pax genes with human disease...

..Once committed to the B-lineage, B cells require Pax5 function to maintain their B-lymphoid identity throughout B cell development...

..Pax5 therefore plays an essential role in B-lineage commitment by suppressing alternative lineage choices...

..Hence, alternative splicing of Pax-8 gene transcripts not only generates six different Pax-8 variants but is also temporally and spatially regulated during early mouse development...

..Together these data indicate that Pax2 and homeodomain proteins directly bind to and cooperatively regulate the mhb enhancer of Pax5...

..These data implicate CDP in cell-lineage specification during hair follicle morphogenesis, which resembles the role of the related Cut protein in specifying cell fates during Drosophila development...

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..These data demonstrate that Pax5 is essential for maintaining the identity and function of B cells during late B lymphopoiesis...

..5. On the basis of these data, we propose that the cooperation of Pax2 and Pax5 is essential for normal functioning of the organizing center at the midbrain-hindbrain junction...

..Differential regulation of two distinct promoters is thus used to determine the ratio between secreted and membrane-bound forms of Fit-1 (T1/ST2) which may modulate signaling in response to IL-1...

..PAX-1 and PAX-7 map to chromosomal regions containing previously assigned disease loci...

..Consequently, the noi mutation of zebrafish is equivalent to combined inactivation of the mouse Pax2 and Pax5 genes with regard to the loss of midbrain-hindbrain boundary development...

..Together, these data demonstrate that the absence of Pax5 arrests adult B lymphopoiesis at an early developmental stage that is unresponsive to pre-BCR signaling...

..During Drosophila embryogenesis, the Pax258 gene is shown to be expressed in the precursor cells of the external sensory organs, thus suggesting a role for Pax258 in the early development of the peripheral nervous system of insects...

..These data suggest that deregulation of PAX-5 gene transcription by the t(9;14)(pl3;q32) translocation contributes to the pathogenesis of small lymphocytic lymphomas with plasmacytoid differentiation...

..All of this evidence indicates that the transcription factor BSAP may not only play an important role in B-cell differentiation but also in neural development and spermatogenesis...

..Together these data demonstrate therefore that B cell development in the Pax-5 deficient bone marrow is arrested at an early pro-B cell stage which is not yet responsive to pre-B cell receptor signaling...

..Toy is therefore required for initiation of ey expression in the embryo and acts through Ey to activate the eye developmental program...

..In contrast, V(H)-to-D(H)J(H) rearrangements were reduced approximately 50-fold in Pax5-deficient pre-BI cells, suggesting a role for Pax5 in the developmental pathway controlling V-to-DJ recombination...

..These data indicate that Pax proteins can be converted from transcriptional activators to repressors through interaction with corepressors of the Groucho protein family...

..These data define a key role for Pax5 in early B lymphopoiesis and midbrain patterning...

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..These data indicate that Pax-5 is able to contact the basal transcription machinery through the TBP-containing initiation factor TFIID, and that its activity can be controlled by the cell cycle-regulated association with Rb...

..These data suggest that deregulated expression of PAX5 correlates positively with cell proliferation and inversely with neuronal differentiation in desmoplastic medulloblastoma...

..Together, these data identify fra-1 as a unique member of the fos gene family which is under positive control by AP-1 activity...

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..In addition, BSAP was found to be the only abundant DNA-binding activity of B-cell nuclear extracts that interacts with the CD19 promoter. Together, this evidence strongly implicates BSAP in the regulation of the CD19 gene...

..One emerging theme is that negative regulatory networks play an important role in suppressing alternative gene programs and their corresponding cell fates throughout B-cell development...

..These data identify Pax5 as a potent oncogene and demonstrate that the T-lymphoid lineage is particularly sensitive to the oncogenic action of Pax5...

..PAX5 has also been implicated in human B cell malignancies, as it is deregulated by chromosomal translocations in a subset of acute lymphoblastic leukemias and non-Hodgkin lymphomas...

..Hence, the transcriptional initiation and B cell-specific expression of Pax5 is entirely consistent with its B cell lineage commitment function...

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..Hence, the transcriptional initiation and B cell-specific expression of Pax5 is entirely consistent with its B cell lineage commitment function...

..Hence, the complete loss of Pax5 in late B cells could initiate lymphoma development and uncovered an extraordinary plasticity of mature peripheral B cells despite their advanced differentiation stage...

..Hence, STAT5 and IL-7 signaling control cell survival and the developmental ordering of immunoglobulin gene rearrangements by suppressing premature Igk recombination in pro-B cells...

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..The same regulators were unable to induce a myeloid lineage switch in Pax5(+/+) pro-B cells, indicating that Pax5 dominates over myeloid transcription factors in B-lymphocytes...

..Together, these data identify Pax2 and Pax8 as critical regulators that specify the nephric lineage...

..Pax5 thereby interfered with T lineage commitment and early thymocyte development by repressing the transcription of the T cell specification gene Notch1...

..These data suggest that Notch1 acts upstream of GATA3 and Tcf1 in early T cell development and regulates Vbeta-DJbeta rearrangements by controlling the chromatin accessibility of Vbeta genes at the TCRbeta locus...

..The pre-BCR was shown to execute its checkpoint function by regulating genes involved in cell proliferation, intracellular signaling, growth factor responsiveness, and V(D)J recombination...

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..These experiments demonstrate a stepwise activation of Pax5 in early lymphopoiesis and provide mechanistic insights into the process of B cell commitment...

..Pax5 subsequently activates locus contraction and distal VH-DJH rearrangements in collaboration with an unknown factor that is present in pro-B cells, but absent in thymocytes...

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..Our results support a model by which Pax5 does not lead to major alterations in chromatin modification, but inhibits transcription by interfering with the action of myeloid transcription factors...

..Hanna et al. (2008) report in a recent issue of Cell that a defined set of transcription factors can reprogram mature B cells back to pluripotent stem cells...

..Together these experiments have uncovered an unanticipated developmental plasticity of lymphocytes, which may account for lineage switches observed in human malignancies...

..Thus, tightly controlled p100 processing and RelB activation is essential for normal B lymphopoiesis and lymphoid/myeloid lineage decision in bone marrow...

..Moreover, absence of GATA-3 turned Notch from a Th2 inducer into a powerful inducer of Th1 differentiation. Therefore, Gata3 is a critical element determining inductive Th2 differentiation and limiting Th1 differentiation by Notch...

..Thus, 2 functionally specialized subsets of pDCs arise in bone marrow from progenitors that diverge from B, T, and NK lineages at an early stage...

..However, even at mature B cell stages, c-fms chromatin is still in a poised conformation and c-fms expression can be re-activated by conditional deletion of the transcription factor Pax5...

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..Finally, excess GABA-mediated inhibition caused dysfunction of central respiratory circuits in Tlx3 mutant mice...

..This induction assay and these unique ES cell lines will be useful for the generation of mesoderm-derived cell populations with implications for future cell therapeutic/integration assays...

..Hence, pericentromeric recruitment and locus 'decontraction' seem to contribute to the initiation and maintenance of allelic exclusion at the Tcrb locus...

..1/Grg4. These data indicate that Pax5 depends on PU.1, acting in cis, for stable recruitment of Grg co-repressors to B-cell-specific genes...

..Therefore, it constitutes a powerful first-line screen for mutations worth fastidious knock-in approaches...