Background: The major histocompatibility complex (MHC) is essential for human immunity and is highly associated with common diseases, including cancer. While the genetics of the MHC has been studied intensively for many decades, very little is known about the epigenetics of this most polymorphic and disease-associated region of the genome.
Methods: To facilitate comprehensive epigenetic analyses of this region, we have generated a genomic tiling array of 2 Kb resolution covering the entire 4 Mb MHC region. The array has been designed to be compatible with chromatin immunoprecipitation (ChIP), methylated DNA immunoprecipitation (MeDIP), array comparative genomic hybridization (aCGH) and expression profiling, including of non-coding RNAs. The array comprises 7832 features, consisting of two replicates of both forward and reverse strands of MHC amplicons and appropriate controls.
Results: Using MeDIP, we demonstrate the application of the MHC array for DNA methylation profiling and the identification of tissue-specific differentially methylated regions (tDMRs). Based on the analysis of two tissues and two cell types, we identified 90 tDMRs within the MHC and describe their characterisation.
Conclusion: A tiling array covering the MHC region was developed and validated. Its successful application for DNA methylation profiling indicates that this array represents a useful tool for molecular analyses of the MHC in the context of medical genomics.
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http://dx.doi.org/10.1186/1755-8794-1-19 | DOI Listing |
Cell
December 2024
HHMI Janelia Research Campus, Ashburn, VA 20147, USA. Electronic address:
Neuronal dendrites must relay synaptic inputs over long distances, but the mechanisms by which activity-evoked intracellular signals propagate over macroscopic distances remain unclear. Here, we discovered a system of periodically arranged endoplasmic reticulum-plasma membrane (ER-PM) junctions tiling the plasma membrane of dendrites at ∼1 μm intervals, interlinked by a meshwork of ER tubules patterned in a ladder-like array. Populated with Junctophilin-linked plasma membrane voltage-gated Ca channels and ER Ca-release channels (ryanodine receptors), ER-PM junctions are hubs for ER-PM crosstalk, fine-tuning of Ca homeostasis, and local activation of the Ca/calmodulin-dependent protein kinase II.
View Article and Find Full Text PDFACS Nano
December 2024
Department of Physics and Soft Materials Research Center, University of Colorado, Boulder, Colorado 80309-0390, United States.
The tiled fiber laser array is a promising architecture for power scaling and mitigation of atmospheric turbulence. Precise tip-tilt detection and steering of the beamlets in the array to guarantee effective overlap in the far-field is essential for high beam qualities. However, the beamlets are tightly coupled in the far-field, making it a major challenge to identify each other.
View Article and Find Full Text PDFCommun Biol
November 2024
Institut für Biologie, Humboldt-Universität zu Berlin, Vergleichende Zoologie, Philippstraße 13, 10115, Berlin, Germany.
Tessellations (surface architectures of arrays of hard tiles) are common in natural and man-made designs. Boxfishes (Ostracioidea) are almost completely encased in a tessellated armor and have evolved a plethora of cross-sectional carapace shapes, yet whether the scutes constructing these exhibit comparable variation is unknown. Using high-resolution microCT and semi-automatic segmentation algorithms, we quantitatively examined thousands of scutes from 13 species of diverse body form.
View Article and Find Full Text PDFbioRxiv
November 2024
Oregon Hearing Research Center, Oregon Health and Science University, Portland, OR 97239, USA.
Auditory cortex encodes information about nonlinear combinations of spectro-temporal sound features. Convolutional neural networks (CNNs) provide an architecture for generalizable encoding models that can predict time-varying neural activity evoked by natural sounds with substantially greater accuracy than established models. However, the complexity of CNNs makes it difficult to discern the computational properties that support their improved performance.
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