K. Cunningham et al., POTENTIAL REGULATORY ELEMENTS FOR GERMLINE TRANSCRIPTION IN OR NEAR MURINE S-GAMMA-1, International immunology, 10(4), 1998, pp. 527-536
We were interested in identifying cis-acting elements that regulate ge
rmline transcription and switch recombination of heavy chain genes. th
e murine gamma 1 heavy chain gene includes two DNase I hypersensitive
sites, which may represent protein:DNA interactions important for germ
line transcription and switch recombination. One DNase hypersensitive
site is at the promoter/l exon boundary (termed 'Site I'); we localize
d a second pair of DNase hypersensitive sites to just 5' of the S(gamm
a)1 region (termed 'Site II'). The DNA region of hypersensitive Site I
I includes a NF-kappa B/Rel binding site and a STAT6 binding site. It
is noteworthy that NF-kappa B and STAT6 are induced by the same agents
(CD40 ligation and IL-4 respectively) that stimulate germline transcr
iption and switch recombination of the murine gamma 1 gene. Transgenes
with the gamma 1 promoter region (DNase hypersensitive Site I), 1(gam
ma)1 and DNase I hypersensitive Site II expressed germline transcripts
with correct regulation, including IL-4 inducibility, However, the le
vel of stable transcripts produced by the transgenes was much lower th
an that of the endogenous gamma 1 gene, a complete 17 kb gamma 1 trans
gene or a derivative of the 17 kb gamma 1 transgene that lacked most o
f C(gamma)1. The promoter/l(gamma)1/Site II transgenes lacked S(gamma)
1 and we found that gamma 1 transgenes that lacked only S(gamma)1 also
expressed germline transcripts with proper regulation, but at a low l
evel. This suggested that the S(gamma)1 region includes positive eleme
nts for regulation of the amount of germline transcripts.