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 ofIl17andIl17fIs Controlled by Conserved Noncoding Sequence 2

Ist Teil von

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

Ort / Verlag

Cambridge: Elsevier Limited

Erscheinungsjahr

2012

Quelle

EZB Electronic Journals Library

Beschreibungen/Notizen

• T helper 17 (Th17) cells specifically transcribe theIl17 andIl17fgenes, which are localized in the same chromosome region, but the underlying mechanism is unclear. Here, we report aciselement that we previously named conserved noncoding sequence 2 (CNS2) physically interacted with bothIl17andIl17fgene 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 theIl17-Il17fgene 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 forIl17and optimalIl17fgene transcription in Th17 cells.