INVASION OF THE CAG TRIPLET REPEATS BY A COMPLEMENTARY PEPTIDE NUCLEIC-ACID INHIBITS TRANSCRIPTION OF THE ANDROGEN RECEPTOR AND TATA-BINDING PROTEIN GENES AND CORRELATES WITH REFOLDING OF AN ACTIVE NUCLEOSOME CONTAINING A UNIQUE AR GENE SEQUENCE
Lc. Boffa et al., INVASION OF THE CAG TRIPLET REPEATS BY A COMPLEMENTARY PEPTIDE NUCLEIC-ACID INHIBITS TRANSCRIPTION OF THE ANDROGEN RECEPTOR AND TATA-BINDING PROTEIN GENES AND CORRELATES WITH REFOLDING OF AN ACTIVE NUCLEOSOME CONTAINING A UNIQUE AR GENE SEQUENCE, The Journal of biological chemistry, 271(22), 1996, pp. 13228-13233
The DNA sequence of the genes for the androgen receptor (AR) and TATA-
binding protein (TBP), like many other genes encoding transcription fa
ctors, contains a series of tandem CAG repeats, Here we explore the ca
pacity of complementary peptide nucleic acids (PNAs) to invade the CAG
triplets of the AR and TBP genes in human prostatic cancer cells and
show that the PNAs readily entered the nuclei of lysolecithin-permeabi
lized cells and effectively inhibited sense transcription of unique AR
and TBP DNA sequences downstream of the site of PNA;DNA hybridization
, but not upstream of that site, These PNAs had Little or no effect on
transcription of the c-myc gene, which lacks a CAG triplet domain. Co
nversely, a PNA complementary to a unique sequence of the c-myc gene d
id not inhibit transcription of the AR or TBP genes but did inhibit c-
myc transcription. Comparisons of PNA effects on sense and antisense t
ranscription of the AR, TBP, and c-myc genes confirm that progression
of the RNA polymerase complex beyond the site of PNA DNA hybridization
is impaired in both directions. Suppression of the AR gene results in
refolding of a transcriptionally active nucleosome containing a uniqu
e 17-mer AR DNA sequence.