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Transcription factor Oct1 and its coactivator OCA-B are selectively required for CD4 memory T cell formation and function

ABSTRACT: Epigenetic changes are crucial for the generation of immunological memory1-4. Failure to generate or maintain these changes will result in poor memory responses. Similarly, augmenting or stabilizing the correct epigenetic states offers a potential method of enhancing immune memory. Yet the transcription factors that regulate these processes are poorly defined, as are the chromatin modifying complexes they recruit and the chromatin modifications they control. Using pathogen infection models and three different mouse models, including a new conditional allele, we find that the widely expressed transcription factor Oct15, and its cofactor OCA-B6,7, are selectively required the in vivo generation of functional CD4 memory. In vitro, both proteins are also required to maintain a poised state at the Il2 target locus in resting but previously stimulated CD4 T cells, and to generate robust Il2 expression upon restimulation. OCA-B is also required for the robust re-expression of other known targets including Il17a, and Ifng. We identify an underlying mechanism involving OCA-B recruitment of the histone lysine demethylase Jmjd1a8 to targets such as Il2 and Ifng. The findings pinpoint Oct1 and OCA-B as unanticipated mediators of CD4 T cell memory.

ORGANISM(S): Mus musculus

PROVIDER: GSE62202 | GEO | 2015/09/17

SECONDARY ACCESSION(S): PRJNA263470

REPOSITORIES: GEO

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Oct1 and OCA-B are Selectively Required for CD4 Memory T Cell Formation and Function (ChIP-seq)

Project description:Epigenetic changes are crucial for the generation of immunological memory. Failure to generate or maintain these changes will result in poor memory responses. Similarly, augmenting or stabilizing the correct epigenetic states offers a potential method of enhancing immune memory. Yet the transcription factors that regulate these processes are poorly defined, as are the target genes they control and they chromatin-modifying complexes they recruit. Using model pathogens and three different mouse models, we find that the widely expressed transcription factor Oct1 and its cofactor OCA-B are selectively required for the in vivo generation of functional CD4 memory. In vitro, both proteins are required to maintain a poised state at the Il2 target locus in resting but previously stimulated CD4 T cells, and to generate robust Il2 expression upon restimulation. Gene expression profiling indicates that OCA-B is also required for the robust re-expression of multiple other targets including Ifng and Il17a. ChIPseq identify multiple differentially expressed direct targets. We identify an underlying mechanism involving OCA-B recruitment of the histone lysine demethylase Jmjd1a to targets such as Il2 and Ifng. The findings pinpoint Oct1 and OCA-B as unanticipated mediators of CD4 T cell memory. Examination of transcription factor occupancy in CD4 T cells upon rest and restimulation.

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