The pathological hallmarks of psoriasis involve alterations in T cell genes associated with transcriptional levels,which are determined by chromatin accessibility.However,to what extent these alterations in T cell transcriptional levels recapitulate the epigenetic features of psoriasis remains unknown.Here,we systematically profiled chromatin accessibility on Th1,Th2,Th1-17,Th17,and Treg cells and found that chromatin remodeling contributes significantly to the pathogenesis of the disease.The chromatin remodeling tendency of different subtypes of Th cells were relatively consistent.Next,we profiled chromatin accessibility and transcriptional dynamics on memory Th/Treg cells.In the memory Th cells,803 increased and 545 decreased chromatin-accessible regions were identified.In the memory Treg cells,713 increased and 1206 decreased chromatin-accessible regions were identified.A total of 54 and 53 genes were differentially expressed in the peaks associated with the memory Th and Treg cells.FOSL1,SPI1,ATF3,NFKB1,RUNX,ETV4,ERG,FLI1,and ETC1 were identified as regulators in the development of psoriasis.The transcriptional regulatory network showed that NFKB1 and RELA were highly connected and central to the network.NFKB1 regulated the genes of CCL3,CXCL2,and IL1RN.Our results provided candidate transcription factors and a foundational framework of the regulomes of the disease.

Zheng Zhang;Lu Liu;Yanyun Shen;Ziyuan Meng;Min Chen;Zhong Lu;Xuejun Zhang

Department of Dermatology,Huashan Hospital,Fudan University,Shanghai 200040,China;Department of Dermatology,No.1 Hospital and Key Laboratory of Dermatology,Ministry of Education,Anhui Medical University,Hefei 230032,China;Department of Dermatology,Dushu Lake Hospital Affiliated to Soochow University,Suzhou 215123,China

医学前沿

[1]Zheng Zhang;Lu Liu;Yanyun Shen;Ziyuan Meng;Min Chen;Zhong Lu;Xuejun Zhang-.Characterization of chromatin accessibility in psoriasis)[J].医学前沿,2022(03):483-495

ETC1,regulomes

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