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Updated: Aug 23, 2025

Genome-wide Analysis of HDAC Inhibitor-mediated Modulation of microRNAs and mRNAs in B Cells Induced to Undergo Class-switch DNA Recombination and Plasma Cell Differentiation
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Nuclear corepressors NCOR1/NCOR2 regulate B cell development, maintain genomic integrity and prevent transformation

Robin D Lee1, Todd P Knutson2, Sarah A Munro2

  • 1Department of Laboratory Medicine and Pathology, Center for Immunology, Masonic Cancer Center, University of Minnesota, Minneapolis, MN, USA.

Nature Immunology
|November 1, 2022
PubMed

Insights

Nuclear corepressors NCOR1 and NCOR2 are crucial for B cell differentiation. Their absence impairs development, enhances leukemic transformation, and correlates with poorer survival in human leukemia.

Area of Science:

  • Immunology
  • Molecular Biology
  • Epigenetics

Background:

  • Nuclear corepressors NCOR1 and NCOR2 regulate gene expression by interacting with transcription factors.
  • These corepressors are implicated in B cell development and chromatin remodeling.

Purpose of the Study:

  • To investigate the role of NCOR1 and NCOR2 in B cell differentiation and transformation.
  • To elucidate the molecular mechanisms by which NCOR1/2 loss impacts B cell development and leukemogenesis.

Main Methods:

  • Mice with Ncor1/2 deletion were used to study B cell differentiation.
  • Analysis included pre-BCR signaling, STAT5-dependent transcription, and gene expression profiling.
  • Whole-genome sequencing and assessment of human leukemia samples were performed.

Main Results:

  • Ncor1/2 deletion impaired B cell differentiation, attenuated pre-BCR signaling, and enhanced STAT5 signaling.
  • NCOR1/2-deficient B cells showed derepression of EZH2-repressed genes, including the p53 pathway.
  • Loss of NCOR1/2 led to aberrant Rag1/Rag2 expression, increased structural variants, and facilitated leukemic transformation in mice.

Conclusions:

  • NCOR1/2 corepressors are critical regulators of B cell differentiation and genomic stability.
  • NCOR1/2 mutations contribute to B cell transformation and are associated with worse outcomes in human leukemia.
  • Understanding NCOR1/2 function provides insights into B cell development and leukemia pathogenesis.

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