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Localized epigenetic changes induced by DH recombination restricts recombinase to DJH junctions.

ABSTRACT: Genes encoding immunoglobulin heavy chains (Igh) are assembled by rearrangement of variable (V(H)), diversity (D(H)) and joining (J(H)) gene segments. Three critical constraints govern V(H) recombination. These include timing (V(H) recombination follows D(H) recombination), precision (V(H) gene segments recombine only to DJ(H) junctions) and allele specificity (V(H) recombination is restricted to DJ(H)-recombined alleles). Here we provide a model for these universal features of V(H) recombination. Analyses of DJ(H)-recombined alleles showed that DJ(H) junctions were selectively epigenetically marked, became nuclease sensitive and bound RAG recombinase proteins, which thereby permitted D(H)-associated recombination signal sequences to initiate the second step of Igh gene assembly. We propose that V(H) recombination is precise, because these changes did not extend to germline D(H) segments located 5' of the DJ(H) junction.

SUBMITTER: Subrahmanyam R

PROVIDER: S-EPMC3685187 | biostudies-literature | 2012 Dec

REPOSITORIES: biostudies-literature

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Localized epigenetic changes induced by DH recombination restricts recombinase to DJH junctions.

Subrahmanyam Ramesh R Du Hansen H Ivanova Irina I Chakraborty Tirtha T Ji Yanhong Y Zhang Yu Y Alt Frederick W FW Schatz David G DG Sen Ranjan R

Nature immunology 20121028 12

Genes encoding immunoglobulin heavy chains (Igh) are assembled by rearrangement of variable (V(H)), diversity (D(H)) and joining (J(H)) gene segments. Three critical constraints govern V(H) recombination. These include timing (V(H) recombination follows D(H) recombination), precision (V(H) gene segments recombine only to DJ(H) junctions) and allele specificity (V(H) recombination is restricted to DJ(H)-recombined alleles). Here we provide a model for these universal features of V(H) recombinatio ...[more]

PMID: 23104096

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Project description:We are reporting on the fabrication and characterization of microscale electromechanical actuators driven by the internal forces induced within the depletion region of a typical pn junction. Depletion region actuators operate based on the modulation of the interactions of the internal electric field and the net space charge within the depletion region of a pn junction by an external potential. In terms of performance, depletion region actuators fall between electrostatic actuators, where a physical gap separates the charges on two electrodes, and piezoelectric actuators, where the separation between the charges is on the order of lattice constants of the material. An analytic model of depletion region actuator response to an applied potential is developed and verified experimentally. The prototype micro-mechanical device utilized the local stresses produced by the depletion region actuators to generate mechanical vibrations at frequencies far below the resonance frequencies of the structure. A laser Doppler vibrometer was used to measure and compare the displacements and vibration patterns caused by the depletion region and electrostatic actuators. Utilizing depletion region actuators neither requires etching of narrow gaps, which is technically challenging nor is there a need for introducing piezoelectric materials into the fabrication process flow. The simple operating principle and the possibility of exploiting the technique for various optimized linear or nonlinear actuation at small scales provide opportunities for precise electro-mechanical transduction for micro- and nano-mechanical devices. These actuators are therefore suited for the co-fabrication of micro- and nano-mechanical systems and microelectronic circuits. Additionally, the produced strains depend only on the depletion region specifications and the excitation voltage and do not scale with device dimensions. As such, depletion region actuators can be candidates for efficient nanoscale electromechanical actuation.

Dataset Information

Localized epigenetic changes induced by DH recombination restricts recombinase to DJH junctions.

Publications

Localized epigenetic changes induced by DH recombination restricts recombinase to DJH junctions.

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