Transcription of Il17 and Il17f Is Controlled by Conserved Noncoding Sequence 2

Xiaohu Wang; Yibing Zhang; Xuexian O. Yang; Roza I. Nurieva; Seon Hee Chang; Sandra S. Ojeda; Hong S. Kang; Kimberly S. Schluns; Jianfang Gui; Anton M. Jetten; Chen Dong

doi:10.1016/j.immuni.2011.10.019

Transcription of Il17 and Il17f Is Controlled by Conserved Noncoding Sequence 2

Xiaohu Wang, Yibing Zhang, Xuexian O. Yang, Roza I. Nurieva, Seon Hee Chang, Sandra S. Ojeda, Hong S. Kang, Kimberly S. Schluns, Jianfang Gui, Anton M. Jetten, Chen Dong

Immunology

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

104 Scopus citations

Abstract

T helper 17 (Th17) cells specifically transcribe the Il17and Il17f genes, which are localized in the same chromosome region, but the underlying mechanism is unclear. Here, we report a cis element that we previously named conserved noncoding sequence 2 (CNS2) physically interacted with both Il17 and Il17f gene promoters and was sufficient for regulating their selective transcription in Th17 cells. Targeted deletion of CNS2 resulted in impaired retinoic acid-related orphan receptor gammat (RORγt)-driven IL-17 expression invitro. CNS2-deficient Tcells also produced substantially decreased amounts of IL-17F. These cytokine defects were associated with defective chromatin remodeling in the Il17-Il17f gene locus, possibly because of effects on CNS2-mediated recruitment of histone-modifying enzymes p300 and JmjC domain-containing protein 3 (JMJD3). CNS2-deficient animals were also shown to be resistant to experimental autoimmune encephalomyelitis (EAE). Our results thus suggest that CNS2is sufficient and necessary for Il17 and optimal Il17f gene transcription in Th17 cells.

Original language	English (US)
Pages (from-to)	23-31
Number of pages	9
Journal	Immunity
Volume	36
Issue number	1
DOIs	https://doi.org/10.1016/j.immuni.2011.10.019
State	Published - Jan 27 2012

ASJC Scopus subject areas

Immunology and Allergy
Immunology
Infectious Diseases

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10.1016/j.immuni.2011.10.019

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@article{7ae9b242da344707a5c7a2d0bc0c86d8,

title = "Transcription of Il17 and Il17f Is Controlled by Conserved Noncoding Sequence 2",

abstract = "T helper 17 (Th17) cells specifically transcribe the Il17and Il17f genes, which are localized in the same chromosome region, but the underlying mechanism is unclear. Here, we report a cis element that we previously named conserved noncoding sequence 2 (CNS2) physically interacted with both Il17 and Il17f gene promoters and was sufficient for regulating their selective transcription in Th17 cells. Targeted deletion of CNS2 resulted in impaired retinoic acid-related orphan receptor gammat (RORγt)-driven IL-17 expression invitro. CNS2-deficient Tcells also produced substantially decreased amounts of IL-17F. These cytokine defects were associated with defective chromatin remodeling in the Il17-Il17f gene locus, possibly because of effects on CNS2-mediated recruitment of histone-modifying enzymes p300 and JmjC domain-containing protein 3 (JMJD3). CNS2-deficient animals were also shown to be resistant to experimental autoimmune encephalomyelitis (EAE). Our results thus suggest that CNS2is sufficient and necessary for Il17 and optimal Il17f gene transcription in Th17 cells.",

author = "Xiaohu Wang and Yibing Zhang and Yang, {Xuexian O.} and Nurieva, {Roza I.} and Chang, {Seon Hee} and Ojeda, {Sandra S.} and Kang, {Hong S.} and Schluns, {Kimberly S.} and Jianfang Gui and Jetten, {Anton M.} and Chen Dong",

note = "Funding Information: We thank the C.D. laboratory members for their help. The work is supported by research grants from NIH (to C.D. and R.I.N.), American Heart Association (to X.O.Y.), and 973 National Basic Research Program of China (2010CB126301). X.W. receives a postdoctoral fellowship from the National Multiple Sclerosis Society, Y.Z. was supported by a fellowship from Chinese Academy of Sciences, and C.D. receives a Research Trust Fellowship from MD Anderson Cancer Center and is a Leukemia and Lymphoma Society Scholar. C.D. and X.W. designed the research and analyzed the data. X.W., Y.Z., X.O.Y., R.I.N., S.H.C., S.S.O., and H.S.K. performed the experiments, and X.W., J.G., K.S.S., A.M.J., and C.D. prepared the manuscript. ",

year = "2012",

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day = "27",

doi = "10.1016/j.immuni.2011.10.019",

language = "English (US)",

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pages = "23--31",

journal = "Immunity",

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T1 - Transcription of Il17 and Il17f Is Controlled by Conserved Noncoding Sequence 2

AU - Wang, Xiaohu

AU - Zhang, Yibing

AU - Yang, Xuexian O.

AU - Nurieva, Roza I.

AU - Chang, Seon Hee

AU - Ojeda, Sandra S.

AU - Kang, Hong S.

AU - Schluns, Kimberly S.

AU - Gui, Jianfang

AU - Jetten, Anton M.

AU - Dong, Chen

N1 - Funding Information: We thank the C.D. laboratory members for their help. The work is supported by research grants from NIH (to C.D. and R.I.N.), American Heart Association (to X.O.Y.), and 973 National Basic Research Program of China (2010CB126301). X.W. receives a postdoctoral fellowship from the National Multiple Sclerosis Society, Y.Z. was supported by a fellowship from Chinese Academy of Sciences, and C.D. receives a Research Trust Fellowship from MD Anderson Cancer Center and is a Leukemia and Lymphoma Society Scholar. C.D. and X.W. designed the research and analyzed the data. X.W., Y.Z., X.O.Y., R.I.N., S.H.C., S.S.O., and H.S.K. performed the experiments, and X.W., J.G., K.S.S., A.M.J., and C.D. prepared the manuscript.

PY - 2012/1/27

Y1 - 2012/1/27

N2 - T helper 17 (Th17) cells specifically transcribe the Il17and Il17f genes, which are localized in the same chromosome region, but the underlying mechanism is unclear. Here, we report a cis element that we previously named conserved noncoding sequence 2 (CNS2) physically interacted with both Il17 and Il17f gene promoters and was sufficient for regulating their selective transcription in Th17 cells. Targeted deletion of CNS2 resulted in impaired retinoic acid-related orphan receptor gammat (RORγt)-driven IL-17 expression invitro. CNS2-deficient Tcells also produced substantially decreased amounts of IL-17F. These cytokine defects were associated with defective chromatin remodeling in the Il17-Il17f gene locus, possibly because of effects on CNS2-mediated recruitment of histone-modifying enzymes p300 and JmjC domain-containing protein 3 (JMJD3). CNS2-deficient animals were also shown to be resistant to experimental autoimmune encephalomyelitis (EAE). Our results thus suggest that CNS2is sufficient and necessary for Il17 and optimal Il17f gene transcription in Th17 cells.

AB - T helper 17 (Th17) cells specifically transcribe the Il17and Il17f genes, which are localized in the same chromosome region, but the underlying mechanism is unclear. Here, we report a cis element that we previously named conserved noncoding sequence 2 (CNS2) physically interacted with both Il17 and Il17f gene promoters and was sufficient for regulating their selective transcription in Th17 cells. Targeted deletion of CNS2 resulted in impaired retinoic acid-related orphan receptor gammat (RORγt)-driven IL-17 expression invitro. CNS2-deficient Tcells also produced substantially decreased amounts of IL-17F. These cytokine defects were associated with defective chromatin remodeling in the Il17-Il17f gene locus, possibly because of effects on CNS2-mediated recruitment of histone-modifying enzymes p300 and JmjC domain-containing protein 3 (JMJD3). CNS2-deficient animals were also shown to be resistant to experimental autoimmune encephalomyelitis (EAE). Our results thus suggest that CNS2is sufficient and necessary for Il17 and optimal Il17f gene transcription in Th17 cells.

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AN - SCOPUS:84862781260

SN - 1074-7613

VL - 36

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EP - 31

JO - Immunity

JF - Immunity

IS - 1

ER -

Transcription of Il17 and Il17f Is Controlled by Conserved Noncoding Sequence 2

Abstract

ASJC Scopus subject areas

MD Anderson CCSG core facilities

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