Chromosome Transfer Activates and Delineates a Locus Control Region for Perforin

Matthew E. Pipkin, Belma Ljutic, Fernando Cruz-Guilloty, Marcela Nouzova, Anjana Rao, Juan Carlos Zúñiga-Pflücker, Mathias G. Lichtenheld

Research output: Contribution to journalArticle

30 Scopus citations

Abstract

Perforin gene (PRF1) transcription regulates perforin expression in NK cells and CTL. Here we identified the locus-wide ensemble of cis-acting sequences that drives PRF1 transcription physiologically. By using chromosome transfer, we revealed that de novo activation of a silent PRF1 locus was controlled by a 150 kb domain comprised of 16 DNase I hypersensitive sites (DHSs). These cis-acting sequences included a locus control region (LCR) and conferred developmentally appropriate and lineage-specific expression of human perforin from BAC transgenes. The LCR included four distal DHSs that were required for perforin expression from its natural locus, and their engineered deletion from the PRF1 BAC transgene abolished LCR function and led to rapid gene silencing. Thus, LCR function is central for regulating the developmental and activation-specific PRF1 promoter activity characteristic of NK cells and CTL.

Original languageEnglish (US)
Pages (from-to)29-41
Number of pages13
JournalImmunity
Volume26
Issue number1
DOIs
StatePublished - Jan 1 2007

Keywords

  • DNA
  • MOLIMMUNO

ASJC Scopus subject areas

  • Immunology and Allergy
  • Infectious Diseases
  • Immunology

Fingerprint Dive into the research topics of 'Chromosome Transfer Activates and Delineates a Locus Control Region for Perforin'. Together they form a unique fingerprint.

  • Cite this

    Pipkin, M. E., Ljutic, B., Cruz-Guilloty, F., Nouzova, M., Rao, A., Zúñiga-Pflücker, J. C., & Lichtenheld, M. G. (2007). Chromosome Transfer Activates and Delineates a Locus Control Region for Perforin. Immunity, 26(1), 29-41. https://doi.org/10.1016/j.immuni.2006.11.009