Chromatin associated protein kinase C- regulates an inducible gene expression program and microRNAs in human T lymphocytes

Elissa Sutcliffe, Karen Bunting, Yi Qing He, Jasmine Li, Chansavath Phetsouphanh, nabila seddiki, Anjum Zafar, Elizabeth Hindmarsh, Christopher Parish, Anthony Kelleher, Russell L. Mcinness, Taya Toshiki, Peter Milburn, Sudha Rao

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Abstract

Studies in yeast demonstrate that signaling kinases have a surprisingly active role in the nucleus, where they tether to chromatin and modulate gene expression programs. Despite these seminal studies, the nuclear mechanism of how signaling kinases control transcription of mammalian genes is in its infancy. Here, we provide evidence for a hitherto unknown function of protein kinase C-theta (PKC-theta), which physically associates with the regulatory regions of inducible immune response genes in human T cells. Chromatin-anchored PKC-theta forms an active nuclear complex by interacting with RNA polymerase II, the histone kinase MSK-1, and the adaptor molecule 14-3-3 zeta. ChIP-on-chip reveals that PKC-theta binds to promoters and transcribed regions of genes, as well as to microRNA promoters that are crucial for cytokine regulation. Our results provide a molecular explanation for the role of PKC-theta not only in normal T cell function, but also in circumstances of its ectopic expression in cancer
Original languageEnglish
Pages (from-to)704-719
Number of pages16
JournalMolecular Cell
Volume41
Issue number6
DOIs
Publication statusPublished - 2011

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MicroRNAs
Protein Kinase C
Chromatin
T-Lymphocytes
Gene Expression
Phosphotransferases
Protamine Kinase
Genes
RNA Polymerase II
Nucleic Acid Regulatory Sequences
Genetic Promoter Regions
Yeasts
Cytokines
Neoplasms

Cite this

Sutcliffe, Elissa ; Bunting, Karen ; He, Yi Qing ; Li, Jasmine ; Phetsouphanh, Chansavath ; seddiki, nabila ; Zafar, Anjum ; Hindmarsh, Elizabeth ; Parish, Christopher ; Kelleher, Anthony ; Mcinness, Russell L. ; Toshiki, Taya ; Milburn, Peter ; Rao, Sudha. / Chromatin associated protein kinase C- regulates an inducible gene expression program and microRNAs in human T lymphocytes. In: Molecular Cell. 2011 ; Vol. 41, No. 6. pp. 704-719.
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abstract = "Studies in yeast demonstrate that signaling kinases have a surprisingly active role in the nucleus, where they tether to chromatin and modulate gene expression programs. Despite these seminal studies, the nuclear mechanism of how signaling kinases control transcription of mammalian genes is in its infancy. Here, we provide evidence for a hitherto unknown function of protein kinase C-theta (PKC-theta), which physically associates with the regulatory regions of inducible immune response genes in human T cells. Chromatin-anchored PKC-theta forms an active nuclear complex by interacting with RNA polymerase II, the histone kinase MSK-1, and the adaptor molecule 14-3-3 zeta. ChIP-on-chip reveals that PKC-theta binds to promoters and transcribed regions of genes, as well as to microRNA promoters that are crucial for cytokine regulation. Our results provide a molecular explanation for the role of PKC-theta not only in normal T cell function, but also in circumstances of its ectopic expression in cancer",
author = "Elissa Sutcliffe and Karen Bunting and He, {Yi Qing} and Jasmine Li and Chansavath Phetsouphanh and nabila seddiki and Anjum Zafar and Elizabeth Hindmarsh and Christopher Parish and Anthony Kelleher and Mcinness, {Russell L.} and Taya Toshiki and Peter Milburn and Sudha Rao",
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Sutcliffe, E, Bunting, K, He, YQ, Li, J, Phetsouphanh, C, seddiki, N, Zafar, A, Hindmarsh, E, Parish, C, Kelleher, A, Mcinness, RL, Toshiki, T, Milburn, P & Rao, S 2011, 'Chromatin associated protein kinase C- regulates an inducible gene expression program and microRNAs in human T lymphocytes', Molecular Cell, vol. 41, no. 6, pp. 704-719. https://doi.org/10.1016/j.molcel.2011.02.030

Chromatin associated protein kinase C- regulates an inducible gene expression program and microRNAs in human T lymphocytes. / Sutcliffe, Elissa; Bunting, Karen; He, Yi Qing; Li, Jasmine; Phetsouphanh, Chansavath; seddiki, nabila; Zafar, Anjum; Hindmarsh, Elizabeth; Parish, Christopher; Kelleher, Anthony; Mcinness, Russell L.; Toshiki, Taya; Milburn, Peter; Rao, Sudha.

In: Molecular Cell, Vol. 41, No. 6, 2011, p. 704-719.

Research output: Contribution to journalArticle

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AB - Studies in yeast demonstrate that signaling kinases have a surprisingly active role in the nucleus, where they tether to chromatin and modulate gene expression programs. Despite these seminal studies, the nuclear mechanism of how signaling kinases control transcription of mammalian genes is in its infancy. Here, we provide evidence for a hitherto unknown function of protein kinase C-theta (PKC-theta), which physically associates with the regulatory regions of inducible immune response genes in human T cells. Chromatin-anchored PKC-theta forms an active nuclear complex by interacting with RNA polymerase II, the histone kinase MSK-1, and the adaptor molecule 14-3-3 zeta. ChIP-on-chip reveals that PKC-theta binds to promoters and transcribed regions of genes, as well as to microRNA promoters that are crucial for cytokine regulation. Our results provide a molecular explanation for the role of PKC-theta not only in normal T cell function, but also in circumstances of its ectopic expression in cancer

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