Diagenode

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.

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

Share this article

Published
January, 2021

Source

Products used in this publication

  • cut and tag antibody icon
    C15410210-50
    CTCF Antibody - ChIP-seq Grade
  • cut and tag antibody icon
    C15410196
    H3K27ac Antibody - ChIP-seq Grade
  • ChIP kit icon
    C01010171
    Auto iDeal ChIP-seq kit for Histones
  • ChIP kit icon
    C01010172
    Auto iDeal ChIP-seq Kit for Transcription Factors
  • ChIP kit icon
    C01010058
    Auto iDeal ChIP-seq Kit for Transcription Factors
  • Compact Automated System
    B03000002
    IP-Star® Compact Automated System
  • Bioruptor Pico
    B01080010
    Bioruptor® Pico 非接触式超声波破碎仪

活动

  • CLEPIC 2022
    Szczecin, Poland
    Jun 8-Jun 10, 2022
  • European Socienty of Human Genetics - ESHG 2022
    Wien, Austria
    Jun 11-Jun 14, 2022
  • Lausanne Genomics Days 2022
    Lausanne, Switzerland
    Jun 16-Jun 17, 2022
 查看所有活动

新闻

 查看所有新闻


The European Regional Development Fund and Wallonia are investing in your future.

Extension of industrial buildings and new laboratories.


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