Pax5-deficient progenitor B (pro-B) cells are thought to be severely defective for recombination of all immunoglobulin heavy chain (IgH) V gene segments, but the mechanism by which Pax5 regulates this process has not been defined. To address this issue, we have examined the assembly of the IgH locus in Pax5-deficient pro-B cells and find, unexpectedly, that 3' IgH V gene segments, which lie closest to the D-J-Cmu region, recombine efficiently, but progressively more distal V gene segments recombine progressively less efficiently. Histone acetylation and germ-line transcription correlate strongly with an open or an accessible chromatin structure thought to be permissive for V(D)J recombination, and defects in recombination are typically accompanied by deficits in these processes. We were therefore surprised to observe that distal V(H) gene segments in Pax5-/- pro-B cells exhibit no defect in these measures of accessibility. The finding of transcribed, histone acetylated gene segments that fail to recombine suggests that a Pax5-dependent regulatory mechanism is required in addition to standard constraints of accessibility to control V(H) gene recombination.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC195966 | PMC |
| http://dx.doi.org/10.1101/gad.1031403 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Multiple myeloma-associated non-crystalline proximal tubulopathy and crystalline cast nephropathy: Biochemical and structural features of disease-causing monoclonal kappa light chains.
FASEB J
January 2025
Department of Hematology, Nephrology, and Rheumatology, Graduate School of Medicine, Akita University, Akita, Japan.
Various tubular diseases in patients with multiple myeloma (MM) are caused by monoclonal immunoglobulin light chains (LCs). However, the physicochemical characteristics of the disease-causing LCs contributing to the onset of MM-associated tubular diseases remain unclear. We herein report a rare case of MM-associated combined tubulopathies: non-crystalline light chain proximal tubulopathy (LCPT) and crystalline light chain cast nephropathy (LCCN).
View Article and Find Full Text PDFTokay gecko tail regeneration involves temporally collinear expression of HOXC genes and early expression of satellite cell markers.
BMC Biol
January 2025
Institute of Biology Leiden, Leiden University, Sylvius Laboratory, Sylviusweg 72, 2333 BE, Leiden, The Netherlands.
Background: Regeneration is the replacement of lost or damaged tissue with a functional copy. In axolotls and zebrafish, regeneration involves stem cells produced by de-differentiation. These cells form a growth zone which expresses developmental patterning genes at its apex.
View Article and Find Full Text PDFStructural polymorphism and diversity of human segmental duplications.
Nat Genet
January 2025
Department of Genome Sciences, University of Washington School of Medicine, Seattle, WA, USA.
Segmental duplications (SDs) contribute significantly to human disease, evolution and diversity but have been difficult to resolve at the sequence level. We present a population genetics survey of SDs by analyzing 170 human genome assemblies (from 85 samples representing 38 Africans and 47 non-Africans) in which the majority of autosomal SDs are fully resolved using long-read sequence assembly. Excluding the acrocentric short arms and sex chromosomes, we identify 173.
View Article and Find Full Text PDFInactivation of GSK3β by Ser phosphorylation prevents thymocyte necroptosis and impacts Tcr repertoire diversity.
Cell Death Differ
January 2025
Department of Immunology and Microbiology, University of Colorado, Anschutz Medical Campus, Aurora, CO, 80045, USA.
The assembly of Tcrb and Tcra genes require double negative (DN) thymocytes to undergo multiple rounds of programmed DNA double-strand breaks (DSBs), followed by their efficient repair. However, mechanisms governing cell cycle checkpoints and specific survival pathways during the repair process remain unclear. Here, we report high-resolution scRNA-seq analyses of individually sorted mouse DN3 and DN4 thymocytes, which reveals a G2M cell cycle checkpoint, in addition to the known G1 checkpoint, during Tcrb and Tcra recombination.
View Article and Find Full Text PDFQuantitative Structural and Compositional Elucidation of Real-World Pharmaceutical Tablet Using Large Field-of-View, Correlative Microscopy-Tomography Techniques and AI-Enabled Image Analysis.
Pharm Res
January 2025
Synthetic Molecule Pharmaceutical Sciences, Genentech, Inc., 1 DNA Way, South San Francisco, CA, 94080, USA.
Purpose: The purpose of this study is to present a correlative microscopy-tomography approach in conjunction with machine learning-based image segmentation techniques, with the goal of enabling quantitative structural and compositional elucidation of real-world pharmaceutical tablets.
Methods: Specifically, the approach involves three sequential steps: 1) user-oriented tablet constituent identification and characterization using correlative mosaic field-of-view SEM and energy dispersive X-ray spectroscopy techniques, 2) phase contrast synchrotron X-ray micro-computed tomography (SyncCT) characterization of a large, representative volume of the tablet, and 3) constituent segmentation and quantification of the imaging data through user-guided, iterative supervised machine learning and deep learning.
Results: This approach was implemented on a real-world tablet containing 15% API and multiple common excipients.
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!