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ZBTB48 is a priming factor regulating B-cell-specific CIITA expression.

Grishma Rane1, Vivian L S Kuan1, Suman Wang2

  • 1Cancer Science Institute of Singapore, National University of Singapore, 117599, Singapore, Singapore.

The EMBO Journal
|November 20, 2024
PubMed
Summary

The study identifies ZBTB48 as a key regulator of MHC class-II (CIITA) expression in B cells. ZBTB48 acts as an on-off switch, controlling CIITA gene activation crucial for adaptive immunity.

Keywords:
B CellCIITAEpigeneticsGene ExpressionMHC II

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Area of Science:

  • Immunology
  • Molecular Biology
  • Genetics

Background:

  • The class-II transactivator (CIITA) is essential for MHC class-II gene expression and adaptive immunity.
  • CIITA expression is regulated by cell type-specific promoters, including the B-cell-specific promoter CIITA pIII.
  • The transcription factors controlling CIITA expression are not fully understood.

Purpose of the Study:

  • To investigate the role of ZBTB48 in the transcriptional regulation of CIITA.
  • To elucidate the mechanism by which ZBTB48 controls CIITA expression in B cells.

Main Methods:

  • ZBTB48 binding assays to CIITA pIII promoter elements.
  • ZBTB48 knockout studies in cell lines and mice.
  • Chromatin accessibility and histone modification analyses (H3K4me3).

Main Results:

  • ZBTB48 directly binds to activating elements within the CIITA pIII promoter.
  • ZBTB48 knockout impairs IFN-γ-induced CIITA/MHC-II expression in non-APC cells.
  • Loss of ZBTB48 silences MHC-II expression in mouse pro-B and immature B cells.
  • ZBTB48 facilitates chromatin opening at CIITA pIII, preceding H3K4me3 marks.

Conclusions:

  • ZBTB48 is a critical transcriptional activator for B-cell-specific CIITA expression.
  • ZBTB48 functions as a molecular switch, priming CIITA pIII for gene activation.
  • This finding advances our understanding of immune response regulation and B-cell development.