{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Cheung KL"],"funding":["NIAID NIH HHS","Colitis-Crohn Foreningen","HHS | NIH | NIAID | Division of Intramural Research","NIH HHS"],"pagination":["e2312111121"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC11067014"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["121(18)"],"pubmed_abstract":["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<sup>+</sup> 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 <i>Il17a/f</i>. Conversely, Hdac7 collaborates with the TF Aiolos and Smrt/Ncor1-Hdac3 corepressors to repress transcription of Th17 negative regulators, including <i>Il2</i>, 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."],"journal":["Proceedings of the National Academy of Sciences of the United States of America"],"pubmed_title":["Class IIa HDAC4 and HDAC7 cooperatively regulate gene transcription in Th17 cell differentiation."],"pmcid":["PMC11067014"],"funding_grant_id":["R01AI124465","579304","S10 OD030463","S10 OD026880","R01 AI124465","R01 AI168004","R01AI168004"],"pubmed_authors":["Zhang F","Tsankov A","Hu Y","Sharma R","Appiah M","Han X","Xu F","LeJeune A","Sun Y","Ren C","Cheung KL","Zhao L","Ghosh AA","Walsh MJ","Jaganathan A","Zhou MM","Wang X","Xiong H"],"additional_accession":[]},"is_claimable":false,"name":"Class IIa HDAC4 and HDAC7 cooperatively regulate gene transcription in Th17 cell differentiation.","description":"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<sup>+</sup> 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 <i>Il17a/f</i>. Conversely, Hdac7 collaborates with the TF Aiolos and Smrt/Ncor1-Hdac3 corepressors to repress transcription of Th17 negative regulators, including <i>Il2</i>, 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.","dates":{"release":"2024-01-01T00:00:00Z","publication":"2024 Apr","modification":"2025-04-04T02:20:52.007Z","creation":"2025-04-04T02:20:52.007Z"},"accession":"S-EPMC11067014","cross_references":{"pubmed":["38657041"],"doi":["10.1073/pnas.2312111121"]}}