Foxn1 regulates key target genes essential for T cell development in postnatal thymic epithelial cells

Saulius Žuklys; Adam Handel; Saule Zhanybekova; Fatima Govani; Marcel Keller; Stefano Maio; Carlos E. Mayer; Hong Ying Teh; Katrin Hafen; Giuseppe Gallone; Thomas Barthlott; Chris P. Ponting; Georg A. Holländer

doi:10.1038/ni.3537

Foxn1 regulates key target genes essential for T cell development in postnatal thymic epithelial cells

Saulius Žuklys, Adam Handel, Saule Zhanybekova, Fatima Govani, Marcel Keller, Stefano Maio, Carlos E. Mayer, Hong Ying Teh, Katrin Hafen, Giuseppe Gallone, Thomas Barthlott, Chris P. Ponting, Georg A. Holländer

Research output: Contribution to journal › Article › peer-review

Abstract

Thymic epithelial cell differentiation, growth and function depend on the expression of the transcription factor Foxn1; however, its target genes have never been physically identified. Using static and inducible genetic model systems and chromatin studies, we developed a genome-wide map of direct Foxn1 target genes for postnatal thymic epithelia and defined the Foxn1 binding motif. We determined the function of Foxn1 in these cells and found that, in addition to the transcriptional control of genes involved in the attraction and lineage commitment of T cell precursors, Foxn1 regulates the expression of genes involved in antigen processing and thymocyte selection. Thus, critical events in thymic lympho-stromal cross-talk and T cell selection are indispensably choreographed by Foxn1.

Original language	English
Pages (from-to)	1206-1215
Number of pages	10
Journal	Nature Immunology
Volume	17
Issue number	10
Early online date	22 Aug 2016
DOIs	https://doi.org/10.1038/ni.3537
Publication status	Published - Oct 2016

Keywords / Materials (for Non-textual outputs)

TRANSCRIPTION FACTOR
REPERTOIRE SELECTION
EXPRESSION
PROTEIN
THYMOCYTES
PROLIFERATION
MEDULLA
PACKAGE
BETA
CCR7

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Accepted author manuscript, 2.49 MB

Chris Ponting
- MRC Human Genetics Unit
- School of Genetics and Cancer - Chair of Medical Bioinformatics
- Institute of Genetics and Cancer
Person: Academic: Research Active

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title = "Foxn1 regulates key target genes essential for T cell development in postnatal thymic epithelial cells",

abstract = "Thymic epithelial cell differentiation, growth and function depend on the expression of the transcription factor Foxn1; however, its target genes have never been physically identified. Using static and inducible genetic model systems and chromatin studies, we developed a genome-wide map of direct Foxn1 target genes for postnatal thymic epithelia and defined the Foxn1 binding motif. We determined the function of Foxn1 in these cells and found that, in addition to the transcriptional control of genes involved in the attraction and lineage commitment of T cell precursors, Foxn1 regulates the expression of genes involved in antigen processing and thymocyte selection. Thus, critical events in thymic lympho-stromal cross-talk and T cell selection are indispensably choreographed by Foxn1.",

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author = "Saulius {\v Z}uklys and Adam Handel and Saule Zhanybekova and Fatima Govani and Marcel Keller and Stefano Maio and Mayer, \{Carlos E.\} and Teh, \{Hong Ying\} and Katrin Hafen and Giuseppe Gallone and Thomas Barthlott and Ponting, \{Chris P.\} and Holl{\"a}nder, \{Georg A.\}",

year = "2016",

month = oct,

doi = "10.1038/ni.3537",

language = "English",

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AU - Žuklys, Saulius

AU - Handel, Adam

AU - Zhanybekova, Saule

AU - Govani, Fatima

AU - Keller, Marcel

AU - Maio, Stefano

AU - Mayer, Carlos E.

AU - Teh, Hong Ying

AU - Hafen, Katrin

AU - Gallone, Giuseppe

AU - Barthlott, Thomas

AU - Ponting, Chris P.

AU - Holländer, Georg A.

PY - 2016/10

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AB - Thymic epithelial cell differentiation, growth and function depend on the expression of the transcription factor Foxn1; however, its target genes have never been physically identified. Using static and inducible genetic model systems and chromatin studies, we developed a genome-wide map of direct Foxn1 target genes for postnatal thymic epithelia and defined the Foxn1 binding motif. We determined the function of Foxn1 in these cells and found that, in addition to the transcriptional control of genes involved in the attraction and lineage commitment of T cell precursors, Foxn1 regulates the expression of genes involved in antigen processing and thymocyte selection. Thus, critical events in thymic lympho-stromal cross-talk and T cell selection are indispensably choreographed by Foxn1.

KW - TRANSCRIPTION FACTOR

KW - REPERTOIRE SELECTION

KW - EXPRESSION

KW - PROTEIN

KW - THYMOCYTES

KW - PROLIFERATION

KW - MEDULLA

KW - PACKAGE

KW - BETA

KW - CCR7

U2 - 10.1038/ni.3537

DO - 10.1038/ni.3537

M3 - Article

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SP - 1206

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JO - Nature Immunology

JF - Nature Immunology

IS - 10

ER -

Foxn1 regulates key target genes essential for T cell development in postnatal thymic epithelial cells

Abstract

Keywords / Materials (for Non-textual outputs)

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Chris Ponting

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