FoxA1 binding to the MMTV LTR modulates chromatin structure and transcription

PH Holmqvist, S Belikov, KS Zaret, Ö Wrange - Experimental cell research, 2005 - Elsevier
PH Holmqvist, S Belikov, KS Zaret, Ö Wrange
Experimental cell research, 2005Elsevier
Novel binding sites for the forkhead transcription factor family member Forkhead box A
(FoxA), previously referred to as Hepatocyte Nuclear Factor 3 (HNF3), were found within the
mouse mammary tumor virus long terminal repeat (MMTV LTR). The effect of FoxA1 on
MMTV LTR chromatin structure, and expression was evaluated in Xenopus laevis oocytes.
Mutagenesis of either of the two main FoxA binding sites showed that the distal site,− 232/−
221, conferred FoxA1-dependent partial inhibition of glucocorticoid receptor (GR) driven …
Novel binding sites for the forkhead transcription factor family member Forkhead box A (FoxA), previously referred to as Hepatocyte Nuclear Factor 3 (HNF3), were found within the mouse mammary tumor virus long terminal repeat (MMTV LTR). The effect of FoxA1 on MMTV LTR chromatin structure, and expression was evaluated in Xenopus laevis oocytes. Mutagenesis of either of the two main FoxA binding sites showed that the distal site, −232/−221, conferred FoxA1-dependent partial inhibition of glucocorticoid receptor (GR) driven MMTV transcription. The proximal FoxA binding segment consisted of two individual FoxA sites at −57/−46 and −45/−34, respectively, that mediated an increased basal MMTV transcription. FoxA1 binding altered the chromatin structure of both the inactive- and the hormone-activated MMTV LTR. Hydroxyl radical foot printing revealed FoxA1-mediated changes in the nucleosome arrangement. Micrococcal nuclease digestion showed the hormone-dependent sub-nucleosome complex, containing ∼120 bp of DNA, to be expanded by FoxA1 binding to the proximal segment into a larger complex containing ∼200 bp. The potential function of the FoxA1-mediated expression of the MMTV provirus for maintenance of expression in different tissues is discussed.
Elsevier
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