The TGGCA protein binds to the MMTV-LTR, the adenovirus origin of replication, and the BK virus enhancer

Abstract

TGGCA-binding proteins are nuclear proteins with high affinity for double-stranded DNA homologous to the prototype recognition sequence 5'YTGGCANNNTGCCAR 3'. Their ubiquitous tissue distribution in higher vertebrates characterizes them as a class of highly conserved proteins which may exert a basic function. To obtain clues to this function, specific binding sites were mapped on three viral genomes. Recognition sites were identified in the enhancer region of the BK virus, in the LTR of the mouse mammary tumor virus, and in the origin of replication of adenovirus 12. The TGGCA-binding protein from HeLa cells appears to be identical to nuclear factor I described by others, which stimulates initiation of adenovirus DNA replication in vitro. However, data from MMTV, BKV, and from cellular genes suggest that this specific protein-DNA interaction may also be involved in the control of gene activity.

Dual function of a nuclear factor I binding site in MMTV transcription regulation

“…The naturally occurring binding site for NF-I upstream of the MMTV promoter (26,41) had been previously shown to participate in the MMTV transcriptional stimulation by glucocorticoid hormones (18,27). Here we show that its function is a dual one: on one hand as an upstream element for the basal, hormone-independent promoter activity, on the other hand as an adjuvant in the hormone response via a synergistic interaction with the proximal glucocorticoid control element.…”

“…In intact cells, an altered reactivity to dimethylsulfoxide following glucocorticoid induction was observed at a TGT sequence close to the GREs at -2.5 kb of the TAT gene (58). In vitro, no cooperative binding of the purified glucocorticoid receptor to the MMTV DNA could be demonstrated (22), nor of NF-I and receptors (26,27). That the NF-I binding site of MMTV DNA, in addition to the promoter/cap site region, is involved in transcriptional activity within the cell was suggested by results of in vivo exonuclease Ill footprinting, where boundaries of protection were observed at -82 and + 12 in glucocorticoid-treated cells (41).…”

“…The other two were more proximally located: One contained the TATA-box (23) and its deletion resulted in both reduction of hormone response and generation of low levels of RNA with heterogeneous start sites. The other overlapped with the binding site for the so-called 'TGGCA-binding protein' (24,25,26,27), a functional equivalent of the ubiquitous nuclear factor I (NF-I; 28,29), which was shown to increase the rate of initiation (33,31,32,29). The fact that both TATA and NF-I elements map in a region that by itself does not provide any hormone response (8,9) suggests that they act in concert with receptor binding sites in the process of transcriptional stimulation by the hormone.…”

DNA-binding specificity and in vivo targets of Caenorhabditis elegans nuclear factor I

“…A remaining central question is why the NFI consensus sequence is specifically over-represented in the genome, while the number of targets bound in vivo is so small. NFI binding sites are found in of a number of viruses and retroviruses in mammals (23), raising the possibility that the worm motif TTGGCA(N) 3 TGCCAA could be remnant of a virus or transposon. Indeed, the NFI motif is present in three C. elegans transposon-related repetitive elements [Ce000087, Ce000337, and Ce000357; wormbase release ws193) (24,25)].…”

TGGCA protein is present in erythroid nuclei and binds within the nuclease‐hypersensitive sites 5′ of the chicken βH‐ and βA‐globin genes

“…However, several observations from our laboratory and of Felsenfeld and co-workers were inconsistent with this idea [4, 61. First, the footprint H and footprint B activities were only detected in erythroid cells and yet TGGCA protein is known to be present in many if not all chicken tissues [9,10]. Secondly, Emerson et al [4] did not detect specific binding of nuclear factor I (NF-I), the human homologue of chicken TGGCA protein [I 11, to aA-globin 5'-flanking sequences by filter binding techniques.…”