TY - JOUR
T1 - Chromosome Transfer Activates and Delineates a Locus Control Region for Perforin
AU - Pipkin, Matthew E.
AU - Ljutic, Belma
AU - Cruz-Guilloty, Fernando
AU - Nouzova, Marcela
AU - Rao, Anjana
AU - Zúñiga-Pflücker, Juan Carlos
AU - Lichtenheld, Mathias G.
PY - 2007/1/1
Y1 - 2007/1/1
N2 - 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.
AB - 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.
KW - DNA
KW - MOLIMMUNO
UR - http://www.scopus.com/inward/record.url?scp=33846200835&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33846200835&partnerID=8YFLogxK
U2 - 10.1016/j.immuni.2006.11.009
DO - 10.1016/j.immuni.2006.11.009
M3 - Article
C2 - 17222571
AN - SCOPUS:33846200835
VL - 26
SP - 29
EP - 41
JO - Immunity
JF - Immunity
SN - 1074-7613
IS - 1
ER -