Format

Send to

Choose Destination
Sci Rep. 2015 Nov 9;5:16355. doi: 10.1038/srep16355.

Reciprocal regulation of RORγt acetylation and function by p300 and HDAC1.

Author information

1
Department of Immunology, Anhui Medical University, Hefei, Anhui, 230032, China.
2
Department of Public Health, Anhui Medical University, Hefei, Anhui, 230032, China.
3
Key Laboratory of Molecular Virology &Immunology, Unit of Molecular Immunology, Institute Pasteur of Shanghai, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, 200031, China.
4
Department of Cardiovascular Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, 230032, China.
5
Department of Microbiology and Parasitology, Anhui Medical University, Hefei, Anhui, 230032, China.
6
Division of Rheumatology, Huashan Hospital, Fudan University, Shanghai 200040, China.

Abstract

T helper 17 (Th17) cells not only play critical roles in protecting against bacterial and fungal infections but are also involved in the pathogenesis of autoimmune diseases. The retinoic acid-related orphan receptor (RORγt) is a key transcription factor involved in Th17 cell differentiation through direct transcriptional activation of interleukin 17(A) (IL-17). How RORγt itself is regulated remains unclear. Here, we report that p300, which has histone acetyltransferase (HAT) activity, interacts with and acetylates RORγt at its K81 residue. Knockdown of p300 downregulates RORγt protein and RORγt-mediated gene expression in Th17 cells. In addition, p300 can promote RORγt-mediated transcriptional activation. Interestingly, the histone deacetylase (HDAC) HDAC1 can also interact with RORγt and reduce its acetylation level. In summary, our data reveal previously unappreciated posttranslational regulation of RORγt, uncovering the underlying mechanism by which the histone acetyltransferase p300 and the histone deacetylase HDAC1 reciprocally regulate the RORγt-mediated transcriptional activation of IL-17.

PMID:
26549310
PMCID:
PMC4817527
DOI:
10.1038/srep16355
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Nature Publishing Group Icon for PubMed Central
Loading ...
Support Center