Postoperative abdominal sepsis induces selective and persistent changes inCTCF binding within the MHC-II region of human monocytes.

Siegler B. et al.

BACKGROUND: Postoperative abdominal infections belong to the most common triggers of sepsis and septic shock in intensive care units worldwide. While monocytes play a central role in mediating the initial host response to infections, sepsis-induced immune dysregulation is characterized by a defective antigen presentation to T-cells via loss of Major Histocompatibility Complex Class II DR (HLA-DR) surface expression. Here, we hypothesized a sepsis-induced differential occupancy of the CCCTC-Binding Factor (CTCF), an architectural protein and superordinate regulator of transcription, inside the Major Histocompatibility Complex Class II (MHC-II) region in patients with postoperative sepsis, contributing to an altered monocytic transcriptional response during critical illness. RESULTS: Compared to a matched surgical control cohort, postoperative sepsis was associated with selective and enduring increase in CTCF binding within the MHC-II. In detail, increased CTCF binding was detected at four sites adjacent to classical HLA class II genes coding for proteins expressed on monocyte surface. Gene expression analysis revealed a sepsis-associated decreased transcription of (i) the classical HLA genes HLA-DRA, HLA-DRB1, HLA-DPA1 and HLA-DPB1 and (ii) the gene of the MHC-II master regulator, CIITA (Class II Major Histocompatibility Complex Transactivator). Increased CTCF binding persisted in all sepsis patients, while transcriptional recovery CIITA was exclusively found in long-term survivors. CONCLUSION: Our experiments demonstrate differential and persisting alterations of CTCF occupancy within the MHC-II, accompanied by selective changes in the expression of spatially related HLA class II genes, indicating an important role of CTCF in modulating the transcriptional response of immunocompromised human monocytes during critical illness.

IP-Star Compact
iDeal ChIP-seq Kit for Transcription Factors
iDeal ChIP-seq Kit for Histones

Share this article

January, 2021


Products used in this publication

  • cut and tag antibody icon
    CTCF Antibody
  • cut and tag antibody icon
    H3K27ac Antibody
  • ChIP kit icon
    Auto iDeal ChIP-seq kit for Histones
  • ChIP kit icon
    Auto iDeal ChIP-seq Kit for Transcription Factors
  • ChIP kit icon
    Auto iDeal ChIP-seq Kit for Transcription Factors
  • Bioruptor Pico
    Bioruptor® Pico sonication device


  • London Calling 2024
    London, UK
    May 21-May 24, 2024
  • Symposium of the Young Scientist Association
    Vienna, Austria
    May 28-May 29, 2024
  • ESHG 2024
    Berlin, Germany
    Jun 1-Jun 4, 2024
  • CLEPIC 2024
    Warsaw, Poland
    Jun 5-Jun 7, 2024
  • EACR 2024
    Rotterdam, Netherlands
    Jun 10-Jun 13, 2024
  • Chromatin meets South 2024
    Marseille, France
    Jun 13-Jun 14, 2024
 See all events


       Site map   |   Contact us   |   Conditions of sales   |   Conditions of purchase   |   Privacy policy   |   Diagenode Diagnostics