Nuclear Factor 1 and Octamer Transcription Factor 1 Binding Preset the Chromatin Structure of the Mouse Mammary Tumor Virus Promoter for Hormone Induction

Abstract

When the mouse mammary tumor virus (MMTV) is integrated into the genome of a mammalian cell, its long terminal repeat (LTR) harbors six specifically positioned nucleosomes. Transcription from the MMTV promoter is regulated by the glucocorticoid hormone via the glucocorticoid receptor (GR). The mechanism of the apparently constitutive nucleosome arrangement has remained unclear. Previous in vitro reconstitution of nucleosome(s) on small segments of the MMTV LTR suggested that the DNA sequence was decisive for the nucleosome arrangement. However, microinjection of MMTV LTR DNA in Xenopus oocytes rendered randomly distributed nucleosomes. This indicated that oocytes lack factor(s) that induces nucleosome positioning at the MMTV LTR in other cells. Here we demonstrate that specific and concomitant binding of nuclear factor 1 (NF1) and octamer factor 1 (Oct1) to their cognate sites within the MMTV promoter induce a partial nucleosome positioning that is an intermediary state between the randomly organized inactive promoter and the hormone and GR-activated promoter containing distinctly positioned nucleosomes. Oct1 and NF1 reciprocally facilitate each other's binding to the MMTV LTR in vivo. The NF1 and Oct1 binding also facilitate hormone-dependent GR-DNA interaction and result in a faster and stronger hormone response. Since NF1 and Oct1 generate an intermediary state of nucleosome positioning and enhance the hormone-induced response, we refer to this as a preset chromatin structure. We propose that this state of NF1 and Oct1-induced chromatin presetting mimics the early step(s) of chromatin remodeling involved in tissue-specific gene expression.

FoxA1 Binding Directs Chromatin Structure and the Functional Response of a Glucocorticoid Receptor-Regulated Promoter

“…Other factors with lower affinity for chromatinized DNA may achieve enhanced binding by cooperative interactions. An example of the latter is the cooperative binding of the octamer transcription factor 1 (Oct1) and nuclear factor 1 (NF1); they reciprocally facilitate each other's constitutive binding to the mouse mammary tumor virus (MMTV) long terminal repeat (LTR), leading to enhanced hormone-dependent glucocorticoid receptor (GR)-DNA interaction (7).…”

“…However, the combined expression of Oct1 and NF1 results in partial nucleosome positioning (7). Addition of GR and glucocorticoid hormone renders a fully activated MMTV LTR, containing six translationally positioned nucleosomes (5).…”

Effects of genetic variation on chromatin structure and the transcriptional machinery: analysis of the IL6 gene locus

“…19 In lymphoblasts, expression of POU2F1 is constitutively high. 20 To explore the possibility that POU2F1 binding to the IL-6 À 6331 T allele may be facilitating an open chromatin formation, we transfected an IL-6-expressing liver cell line containing the IL6 À 6331T allele, Huh7, which expresses low basal levels of POU2F1, with a POU2F1 expression vector.…”

Nuclear Factor 1 and T-Cell Factor/LEF Recognition Elements Regulate Pitx2 Transcription in Pituitary Development

“…In this system, NF-1 is required for full transcriptional activity by stabilizing the chromatin structure and allowing other factors to bind (15). In Xenopus oocytes, NF-1 cooperates with Oct-1 to stabilize an intermediate chromatin structure and likely acts as a platform to recruit other factors (3,4). Consistent with this notion, NF-1 has been shown to occupy the glial fibrillary acidic protein promoter prior to the differentiation of astrocytes and cooperates with AP1 in astrocytes to regulate gene expression but fails to activate expression …”