Open AccessELF3 activated by a superenhancer and an autoregulatory feedback loop is required for high-level HLA-C expression on extravillous trophoblasts
Author(s) -
Qin Li,
Torsten Meißner,
Fang Wang,
Ziwei Du,
Sai Ma,
Sarika Kshirsagar,
Tamara Tilburgs,
Jason D. Buenrostro,
Motonari Uesugi,
Jack L. Strominger
Publication year - 2021
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.2025512118
Subject(s) - biology , hla g , trophoblast , promoter , gene expression , regulation of gene expression , human leukocyte antigen , microbiology and biotechnology , pregnancy , gene , genetics , placenta , fetus , antigen
Significance Several techniques have identified ELF3 as particularly important in regulating trophoblast-specific HLA-C expression. This results from a single-nucleotide difference in the promotor of the HLA-C gene at the RFX5 binding site that creates an ELF3 binding site not found in the HLA-A or HLA-B promoters. We discovered a superenhancer and a positive autoregulatory feedback loop that promotes expression of the ELF3 gene in trophoblasts. Disruption of either the superenhancer by (+)-JQ1 or interference with the positive-feedback loop by wrenchnolol decreased ELF3 levels, and thus HLA-C expression. Aberrations of this complex regulatory system could be involved in control of infection, miscarriage, preterm birth, preeclampsia, as well as parturition in normal pregnancy and in development of choriocarcinoma.