Class IIa HDAC4 and HDAC7 cooperatively regulate gene transcription in Th17 cell differentiation.

Autor:	Cheung KL; Department of Pharmacological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029., Zhao L; Institute of Epigenetic Medicine of the First Hospital, Jilin University, Changchun 130061, China., Sharma R; Department of Pharmacological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029., Ghosh AA; Department of Pharmacological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029., Appiah M; Department of Pharmacological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029., Sun Y; Department of Pharmacological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029., Jaganathan A; Department of Pharmacological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029., Hu Y; Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029., LeJeune A; Department of Pharmacological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029., Xu F; Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029., Han X; Institute of Epigenetic Medicine of the First Hospital, Jilin University, Changchun 130061, China., Wang X; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029., Zhang F; Department of Pediatrics, Icahn School of Medicine at Mount Sinai, New York, NY 10029., Ren C; Department of Pharmacological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029., Walsh MJ; Department of Pharmacological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029., Xiong H; Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029., Tsankov A; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029., Zhou MM; Department of Pharmacological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029.
Jazyk:	angličtina
Zdroj:	Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2024 Apr 30; Vol. 121 (18), pp. e2312111121. Date of Electronic Publication: 2024 Apr 24.
DOI:	10.1073/pnas.2312111121
Abstrakt:	Class II histone deacetylases (HDACs) are important in regulation of gene transcription during T cell development. However, our understanding of their cell-specific functions is limited. In this study, we reveal that class IIa Hdac4 and Hdac7 (Hdac4/7) are selectively induced in transcription, guiding the lineage-specific differentiation of mouse T-helper 17 (Th17) cells from naive CD4 + T cells. Importantly, Hdac4/7 are functionally dispensable in other Th subtypes. Mechanistically, Hdac4 interacts with the transcription factor (TF) JunB, facilitating the transcriptional activation of Th17 signature genes such as Il17a/f . Conversely, Hdac7 collaborates with the TF Aiolos and Smrt/Ncor1-Hdac3 corepressors to repress transcription of Th17 negative regulators, including Il2 , in Th17 cell differentiation. Inhibiting Hdac4/7 through pharmacological or genetic methods effectively mitigates Th17 cell-mediated intestinal inflammation in a colitis mouse model. Our study uncovers molecular mechanisms where HDAC4 and HDAC7 function distinctively yet cooperatively in regulating ordered gene transcription during Th17 cell differentiation. These findings suggest a potential therapeutic strategy of targeting HDAC4/7 for treating Th17-related inflammatory diseases, such as ulcerative colitis. Competing Interests: Competing interests statement:The authors declare no competing interest.
Databáze:	MEDLINE
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