Details

Autor(en) / Beteiligte

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

Titel

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

Ist Teil von

• Immunity (Cambridge, Mass.), 2012-01, Vol.36 (1), p.23-31

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2012

Quelle

Free E-Journal (出版社公開部分のみ）

Beschreibungen/Notizen

• T helper 17 (Th17) cells specifically transcribe the Il17 and 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 in vitro. CNS2-deficient T cells 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 CNS2 is sufficient and necessary for Il17 and optimal Il17f gene transcription in Th17 cells. ► CNS2 is sufficient to drive expression of both IL-17 and IL-17F in Th17 cells ► CNS2 is indispensible for lineage-specific expression of IL-17 ► CNS2 interacts with the Il17 and Il17f promoters in a cell-type-specific manner ► CNS2 modulates the chromatin accessibility of the Th17 cytokine gene locus