Transcription-dependent mobilization of nucleosomes at accessible TCR gene segments in vivo

Hrisavgi D. Kondilis-Mangum, Robin Milley Cobb, Oleg Osipovich, Sruti Srivatsan, Eugene M. Oltz, Michael S. Krangel

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Abstract

Accessibility of chromosomal recombination signal sequences to the RAG protein complex is known to be essential for V(D)J recombination at Ag receptor loci in vivo. Previous studies have addressed the roles of cis-acting regulatory elements and germline transcription in the covalent modification of nucleosomes at Ag receptor loci. However, a detailed picture of nucleosome organization at accessible and inaccessible recombination signal sequences has been lacking. In this study, we have analyzed the nucleosome organization of accessible and inaccessible Tcrb and Tcra alleles in primary murine thymocytes in vivo. We identified highly positioned arrays of nucleosomes at Dβ, J β, and Jα segments and obtained evidence indicating that positioning is established at least in part by the regional DNA sequence. However, we found no consistent positioning of nucleosomes with respect to recombination signal sequences, which could be nucleosomal or internucleosomal even in their inaccessible configurations. Enhancer- and promoter-dependent accessibility was characterized by diminished abundance of certain nucleosomes and repositioning of others. Moreover, some changes in nucleosome positioning and abundance at Jα61 were shown to be a direct consequence of germline transcription. We suggest that enhancer- and promoter-dependent transcription generates optimal recombinase substrates in which some nucleosomes are missing and others are covalently modified.

Original languageEnglish
Pages (from-to)6970-6977
Number of pages8
JournalJournal of Immunology
Volume184
Issue number12
DOIs
StatePublished - Jun 15 2010

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    Kondilis-Mangum, H. D., Cobb, R. M., Osipovich, O., Srivatsan, S., Oltz, E. M., & Krangel, M. S. (2010). Transcription-dependent mobilization of nucleosomes at accessible TCR gene segments in vivo. Journal of Immunology, 184(12), 6970-6977. https://doi.org/10.4049/jimmunol.0903923