Some Integrable Systems in Nonlinear Quantum Optics

In the paper we investigate the theory of quantum optical systems. As an application we integrate and describe the quantum optical systems which are generically related to the classical orthogonal polynomials. The family of coherent states related to these systems is constructed and described. Some applications are also presented.Comment: 27 page

EBF1-deficient bone marrow stroma elicits persistent changes in HSC potential

Crosstalk between mesenchymal stromal cells (MSCs) and hematopoietic stem cells (HSCs) is essential for hematopoietic homeostasis and lineage output. Here, we investigate how transcriptional changes in bone marrow (BM) MSCs result in long-lasting effects on HSCs. Single-cell analysis of Cxcl12-abundant reticular (CAR) cells and PDGFRα+Sca1+ (PαS) cells revealed an extensive cellular heterogeneity but uniform expression of the transcription factor gene Ebf1. Conditional deletion of Ebf1 in these MSCs altered their cellular composition, chromatin structure and gene expression profiles, including the reduced expression of adhesion-related genes. Functionally, the stromal-specific Ebf1 inactivation results in impaired adhesion of HSCs, leading to reduced quiescence and diminished myeloid output. Most notably, HSCs residing in the Ebf1-deficient niche underwent changes in their cellular composition and chromatin structure that persist in serial transplantations. Thus, genetic alterations in the BM niche lead to long-term functional changes of HSCs

EBF1 is continuously required for stabilizing local chromatin accessibility in pro-B cells

The establishment of de novo chromatin accessibility in lymphoid progenitors requires the "pioneering" function of transcription factor (TF) early B cell factor 1 (EBF1), which binds to naïve chromatin and induces accessibility by recruiting the BRG1 chromatin remodeler subunit. However, it remains unclear whether the function of EBF1 is continuously required for stabilizing local chromatin accessibility. To this end, we replaced EBF1 by EBF1-FKBPF36V in pro-B cells, allowing the rapid degradation by adding the degradation TAG13 (dTAG13) dimerizer. EBF1 degradation results in a loss of genome-wide EBF1 occupancy and EBF1-targeted BRG1 binding. Chromatin accessibility was rapidly diminished at EBF1-binding sites with a preference for sites whose occupancy requires the pioneering activity of the C-terminal domain of EBF1. Diminished chromatin accessibility correlated with altered gene expression. Thus, continuous activity of EBF1 is required for the stable maintenance of the transcriptional and epigenetic state of pro-B cells

Integrin β1 regulates marginal zone B cell differentiation and PI3K signaling

Marginal zone (MZ) B cells represent innate-like B cells that mediate a fast immune response. The adhesion of MZ B cells to the marginal sinus of the spleen is governed by integrins. Here, we address the question of whether β1-integrin has additional functions by analyzing Itgb1fl/flCD21Cre mice in which the β1-integrin gene is deleted in mature B cells. We find that integrin β1–deficient mice have a defect in the differentiation of MZ B cells and plasma cells. We show that integrin β1–deficient transitional B cells, representing the precursors of MZ B cells, have enhanced B cell receptor (BCR) signaling, altered PI3K and Ras/ERK pathways, and an enhanced interaction of integrin-linked kinase (ILK) with the adaptor protein Grb2. Moreover, the MZ B cell defect of integrin β1–deficient mice could, at least in part, be restored by a pharmacological inhibition of the PI3K pathway. Thus, β1-integrin has an unexpected function in the differentiation and function of MZ B cells

Genetic interaction between Lef1 and Alx4 is required for early embryonic development

Lymphoid Enhancer Factor-1 (Lef1) facilitates the assembly of transcriptional regulatory complexes and mediates nuclear responses to Wnt signals. We determined previously that the mesenchymally restricted, paired-like homeodomain protein Aristaless-like 4 (Alx4) interacts with Lef1 and together alters promoter activity of candidate genes. In order to define their overlapping functions, mice deficient for both Lef1 and Alx4 activity (Lef1^-/-/Alx4^lstD/lstD) were produced. Whereas embryos lacking either Lef1 or Alx4 activity remain viable up to or after birth, early embryonic lethality results when both factors were absent. No viable Lef1^-/-/Alx4^lstD/lstD embryos were recovered beyond 9.5 dpc. Between E8.5 and E10, viable Lef1^-/-/Alx4^lstD/lstD embryos were developmentally delayed 0.5 days relative to littermates of all other genotypes. Principle among the alterations seen in Lef1^-/-/Alx4^lstD/lstD animals was defective vasculature in both embryonic and extra-embryonic tissues. In the yolk sac, while the vascular network is present, it were greatly diminished and large vitelline vessels were largely absent. Platelet/endothelial cell adhesion molecule (PECAM) staining revealed that the major vessels in the head of compound mutant embryos were absent, while the other vessels were finer than those seen in normal littermates. Pools of blood and pericardial effusion were also apparent in Lef1^-/-/Alx4^lstD/lstD animals, further indicative of a defective vasculature. These data confirm genetically the interaction between Lef1 and Alx4 and further reveal unknown, overlapping roles for these transcription factors in embryonic vasculogenesis

Identification of the regions involved in DNA binding by the mouse PEBP2α protein

AbstractThe polyomavirus enhancer binding protein 2α (PEBP2α) is a DNA binding transcriptional regulatory protein that binds conserved sites in the polyomavirus enhancer, mammalian type C retroviral enhancers and T-cell receptor gene enhancers. Binding of PEBP2α and homologous proteins to the consensus DNA sequence TGPyGGTPy is mediated through a protein domain known as the runt domain. Although recent NMR studies of DNA-bound forms of the runt domain have shown an immunoglobulin-like (Ig) fold, the identification of residues of the protein that are involved in DNA binding has been obscured by the low solubility of the runt domain. Constructs of the mouse PEBP2αA1 gene were generated with N- and C-terminal extensions beyond the runt homology region. The construct containing residues Asp90 to Lys225 of the sequence (PEBP2α90–225) yielded soluble protein. The residues that participate in DNA binding were determined by comparing the NMR spectra of free and DNA-bound PEBP2α90–225. Analysis of the changes in the NMR spectra of the two forms of the protein by chemical shift deviation mapping allowed the unambiguous determination of the regions that are responsible for specific DNA recognition by PEBP2α. Five regions in PEBP2α90–225 that are localized at one end of the β-barrel were found to interact with DNA, similar to the DNA binding interactions of other Ig fold proteins

Satb2 Regulates Callosal Projection Neuron Identity in the Developing Cerebral Cortex

SummarySatb2 is a DNA-binding protein that regulates chromatin organization and gene expression. In the developing brain, Satb2 is expressed in cortical neurons that extend axons across the corpus callosum. To assess the role of Satb2 in neurons, we analyzed mice in which the Satb2 locus was disrupted by insertion of a LacZ gene. In mutant mice, β-galactosidase-labeled axons are absent from the corpus callosum and instead descend along the corticospinal tract. Satb2 mutant neurons acquire expression of Ctip2, a transcription factor that is necessary and sufficient for the extension of subcortical projections by cortical neurons. Conversely, ectopic expression of Satb2 in neural stem cells markedly decreases Ctip2 expression. Finally, we find that Satb2 binds directly to regulatory regions of Ctip2 and induces changes in chromatin structure. These data suggest that Satb2 functions as a repressor of Ctip2 and regulatory determinant of corticocortical connections in the developing cerebral cortex

Two Regulatory Elements for Immunoglobulin kappa Light Chain Gene Expression

By using internal deletions within a rearranged immunoglobulin kappa light chain gene, the presence of an intron regulatory sequence (enhancer) has been confirmed. Its presence is required for high-level transcription from a plasmid after transfection into myeloma cells. Transfection efficiency was monitored by the activity of a deleted H4 histone gene included in the plasmid. The intron element could be moved upstream of the gene in both orientations, fulfilling the definition of an enhancer. By using 5' deletions, a second regulatory element was located upstream of the "TATA" box, between positions -69 and -104. These two elements both are required for efficient kappa chain gene expression

EBF1 promotes triple-negative breast cancer progression by surveillance of the HIF1α pathway

Early B cell factor 1 (EBF1) is a transcriptional factor with a variety of roles in cell differentiation and metabolism. However, the functional roles of EBF1 in tumorigenesis remain elusive. Here, we demonstrate that EBF1 is highly expressed in triple-negative breast cancer (TNBC). Furthermore, EBF1 has a pivotal role in the tumorigenicity and progression of TNBC. Moreover, we found that depletion of EBF1 induces extensive cell mitophagy and inhibits tumor growth. Genome-wide mapping of the EBF1 transcriptional regulatory network revealed that EBF1 drives TNBC tumorigenicity by assembling a transcriptional complex with HIF1α that fine-tunes the expression of HIF1α targets via suppression of p300 activity. EBF1 therefore holds HIF1α activity in check to avert extensive mitophagy-induced cell death. Our findings reveal a key function for EBF1 as a master regulator of mitochondria homeostasis in TNBC and indicate that targeting this pathway may offer alternative treatment strategies for this aggressive subtype of breast cancer