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Unknown,Transcriptomics,Genomics,Proteomics

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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. Examination of 4 different conditions in 2 genotypes

ORGANISM(S): Mus musculus

SUBMITTER: Dean Tantin

PROVIDER: E-GEOD-62202 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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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.

2015-09-17 | E-GEOD-65918 | biostudies-arrayexpress

Oct1 and OCA-B are Selectively Required for CD4 Memory T Cell Formation and Function

Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

2015-09-17 | E-GEOD-65925 | biostudies-arrayexpress

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Transcription profiling of mouse effector cells derived from naive or central memory pmel-1 CD8+ T cells

Project description:Effector cells for adoptive immunotherapy can be generated by in vitro stimulation of naÃ¯ve or memory subsets of CD8+ T cells. While the characteristics of CD8+ T cell subsets are well defined, the heritable influence of those populations on their effector cell progeny is not well understood. We studied effector cells generated from naÃ¯ve or central memory CD8+ T cells and found that they retained distinct gene expression signatures and developmental programs. Effector cells derived from central memory cells tended to retain their CD62L+ phenotype, but also to acquire KLRG1, an indicator of cellular senescence. In contrast, the effector cell progeny of naÃ¯ve cells displayed reduced terminal differentiation, and, following infusion, they displayed greater expansion, cytokine production, and tumor destruction. These data indicate that effector cells retain a gene expression imprint conferred by their naÃ¯ve or central memory progenitors, and they suggest a strategy for enhancing cancer immunotherapy. Experiment Overall Design: Effector cells were generated from naive or central memory CD8+ T cells. The cells were then rested (unstimulated) or restimulated (stimulated). This experimental design resulted in 4 groups (NaÃ¯ve-derived/stimulated, NaÃ¯ve-derived/unstimulated, Central memory-derived/stimulated, Central memory-derived/unstimulated). Three replicates from independent experiments were analyzed.

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

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

Project description: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.

2015-09-17 | GSE62202 | GEO

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2013-03-07 | E-GEOD-43956 | biostudies-arrayexpress

Direct regulation of T cell exhaustion by NFAT

Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

2015-02-13 | E-GEOD-64409 | biostudies-arrayexpress

Direct regulation of T cell exhaustion by NFAT [ChIP-Seq]

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2015-02-13 | E-GEOD-64407 | biostudies-arrayexpress

Tuberous sclerosis complex 1 (Tsc1) enforces quiescence of naive T cells to promote immune homeostasis and function

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