475 High resolution chromatin loops associate with gene targets for psoriasis susceptibility regions
نویسندگان
چکیده
There are over 80 psoriasis-associated loci identified, with a majority playing regulatory roles; however, their gene targets yet to be identified. Chromatin loops play an important role in regulation, and can detected by chromosome conformation capture techniques like Hi-C. In this study, we deep sequenced Hi-C libraries (∼1 billion reads/reaction) generate nine PBMC-derived subsets from 2 individuals (∼50,000 cells each): 4 unstimulated CD3+CD45RO+ memory T (CD4+CLA-, CD4+CLA+, CD8+CLA-, CD8+CLA+); the same after 24 hours of CD3/CD28 stimulation CD1c- (primarily cells); mDC. Using 5k-10k contact map resolution, identified 13,186 ± 2,857 per library, ranging 30 1,980 kb long, using Mustache. Notably, found that ∼50% have at least one end overlapping transcription start site, providing unique resource for mapping long-range promoter interactions immunocytes. We 27 6 library linked promoters whose loop ends could also mapped known psoriasis signals, defined 95% credible intervals generated recent transethnic GWAS (HGG Adv 2022). Of 47 target genes involved such loops, 8 previously suggested psoriasis: ANXA6, ELMO1, ETS1, FASLG, MBD2, IFI44, PTGER4 STARD6. Among them, FASLG IFI44 were present only cells, while rest presented both further revealed other candidates including KAT5, NHLRC3/PROSER1, SUCO, which signals through multiple This study provides complementary support psoriasis-related level 3D genome structure, nominates interest future studies.
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ژورنال
عنوان ژورنال: Journal of Investigative Dermatology
سال: 2022
ISSN: ['1523-1747', '0022-202X']
DOI: https://doi.org/10.1016/j.jid.2022.05.484