Histone acetylation characterizes chromatin presetting by NF1 and Oct1 and enhances glucocorticoid receptor binding to the MMTV promoter.
Transcription from the mouse mammary tumor virus (MMTV) promoter is induced by the glucocorticoid receptor (GR). This switch was reconstituted in Xenopus oocytes. Previously, we showed that Nuclear Factor 1 (NF1) and Octamer Transcription Factor 1 (Oct1) bind constitutively to the MMTV promoter and thereby induce translational nucleosome positioning representing an intermediary, i.e. preset, state of nucleosome organization. Here we further characterize this NF1 and Oct1 induced preset chromatin in relation to the inactive and the hormone-activated state. The preset chromatin exhibits increased histone acetylation but does not cause dissociation of histone H1 as oppose to the hormone-activated state. Furthermore, upon hormone induction the preset MMTV chromatin displays an enhanced and prolonged GR binding capacity and transcription during an intrinsic and time-dependent silencing of the injected template. The silencing process correlates with a reduced histone acetylation. However, a histone deacetylase inhibitor, trichostatin A (TSA), does not counteract silencing in spite of its distinct stimulation of GR-DNA binding. The latter indicates the importance of histone acetylation to maintain DNA access for inducible factor binding. We discuss how constitutively bound factors such as NF1 and Oct1 may participate in the maintenance of tissue specificity of hormone responsive genes.
Astrand
Carolina
C
Department of Cell and Molecular Biology, Karolinska Institutet, Stockholm, Sweden. ca340@cam.ac.uk
Belikov
Sergey
S
Wrange
Orjan
O
D000107:Acetylation; D000818:Animals; D002843:Chromatin / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000378:metabolism; D020868:Gene Silencing; D005938:Glucocorticoids / Q000819:agonists / Q000378:metabolism; D056572:Histone Deacetylase Inhibitors; D006655:Histone Deacetylases / Q000378:metabolism; D006657:Histones / Q000378:metabolism*; D006801:Humans; D006877:Hydroxamic Acids / Q000378:metabolism; D008324:Mammary Tumor Virus, Mouse / Q000235:genetics / Q000378:metabolism; D008745:Methylation; D051379:Mice; D051839:NFI Transcription Factors / Q000378:metabolism*; D050811:Octamer Transcription Factor-1 / Q000378:metabolism*; D009865:Oocytes / Q000166:cytology / Q000502:physiology; D011401:Promoter Regions, Genetic; D051381:Rats; D011965:Receptors, Glucocorticoid / Q000378:metabolism*; D013552:Swine; D015533:Transcriptional Activation; D014982:Xenopus laevis
D002843:Chromatin; D004791:Enzyme Inhibitors; D005938:Glucocorticoids; D056572:Histone Deacetylase Inhibitors; D006657:Histones; D006877:Hydroxamic Acids; D051839:NFI Transcription Factors; D050811:Octamer Transcription Factor-1; D011965:Receptors, Glucocorticoid; C012589:trichostatin A; D006655:Histone Deacetylases