Unique Immune Cell Coactivators Specify Locus Control Region Function and Cell Stage. Academic Article uri icon

Overview

abstract

  • Locus control region (LCR) functions define cellular identity and have critical roles in diseases such as cancer, although the hierarchy of structural components and associated factors that drive functionality are incompletely understood. Here we show that OCA-B, a B cell-specific coactivator essential for germinal center (GC) formation, forms a ternary complex with the lymphoid-enriched OCT2 and GC-specific MEF2B transcription factors and that this complex occupies and activates an LCR that regulates the BCL6 proto-oncogene and is uniquely required by normal and malignant GC B cells. Mechanistically, through OCA-B-MED1 interactions, this complex is required for Mediator association with the BCL6 promoter. Densely tiled CRISPRi screening indicates that only LCR segments heavily bound by this ternary complex are essential for its function. Our results demonstrate how an intimately linked complex of lineage- and stage-specific factors converges on specific and highly essential enhancer elements to drive the function of a cell-type-defining LCR.

publication date

  • November 23, 2020

Research

keywords

  • B-Lymphocytes
  • Germinal Center
  • Locus Control Region

Identity

PubMed Central ID

  • PMC7737631

Scopus Document Identifier

  • 85097310776

Digital Object Identifier (DOI)

  • 10.1186/s12859-017-1708-7

PubMed ID

  • 33232656

Additional Document Info

volume

  • 80

issue

  • 5