BBSRC DTA Studentship: Large-scale chromatin remodelling of immunoglobulin loci - a paradigm for multigene regulation

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The human immune system fights infections by the generation of proteins called antibodies (immunoglobulins) that recognize and eliminate bacteria and viruses. To recognize the millions of potential infectious agents, groups of genes in the immunoglobulin DNA sequences are cut and pasted together into many different combinations in a process called V(D)J recombination. These DNA sequences are enormous, containing 200 genes, but all must be made available at the same time, so the immune system has evolved several large-scale processes that unwind the DNA to allow cutting and pasting. We have discovered that large non-coding RNAs (that don't make protein) are generated from the immunoglobulin heavy chain DNA sequence before V(D)J recombination, and we are testing the hypothesis that the process of transcription which generates these RNAs unwinds this enormous DNA sequence. This research will increase our understanding of how antibodies are made normally, and also of the causes of the failure to make enough antibodies to fight infection, which underlies several immunodeficiency diseases.

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