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Author Notes:

Jeremy M. Boss: jmboss@emory.edu

We thank the members of the Boss lab for their helpful critiques and suggestions.

The authors declare no competing financial interest in relation to the work described.

Subjects:

Research Funding:

This work was supported by the National Institutes of Health grants RO1GM47310 and T32GM0008490.

Keywords:

  • Science & Technology
  • Life Sciences & Biomedicine
  • Genetics & Heredity
  • Immunology
  • CLASS-II TRANSACTIVATOR
  • REGULATORY ELEMENTS
  • GENE-EXPRESSION
  • IFN-GAMMA
  • MHC
  • PROMOTER
  • TRANSCRIPTION
  • ENHANCERS
  • DIFFERENTIATION
  • DISTINCT

Common distal elements orchestrate CIITA isoform-specific expression in multiple cell types

Tools:

Journal Title:

Genes and Immunity

Volume:

Volume 15, Number 8

Publisher:

, Pages 543-555

Type of Work:

Article | Post-print: After Peer Review

Abstract:

Major histocompatibility class II (MHC-II) expression is critical for immune responses and is controlled by the MHC-II transactivator CIITA. CIITA is primarily regulated at the transcriptional level and is expressed from three main promoters with myeloid, lymphoid and interferon (IFN)-γ-treated non-hematopoietic cells using promoters pI, pIII and pIV, respectively. Recent studies in non-hematopoietic cells suggest that a series of distal regulatory elements may be involved in regulating CIITA transcription. To identify distal elements in B cells, a DNase I hypersensitivity screen was performed, revealing a series of potential novel regulatory elements. These elements were analyzed computationally and biochemically. Several regions displayed active histone modifications and/or enhanced expression of a reporter gene. Four of the elements interacted with pIII in B cells. These same four regions were also found to interact with pI in splenic dendritic cells (spDC). Intriguingly, examination of the above interactions in pI-knockout-derived spDC showed a switch to the next available promoter, pIII. Extensive DNA methylation was found at the pI region in B cells, suggesting that this promoter is not accessible in B cells. Thus, CIITA expression is likely mediated in hematopoietic cells by common elements with promoter accessibility having a part in promoter choice.

Copyright information:

© 2014 Macmillan Publishers Limited All rights reserved.

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