TY - JOUR

T1 - Genome-wide identification of estrogen receptor alpha-binding sites in mouse liver.

AU - Gao, Hui

AU - Fält, Susann

AU - Sandelin, Albin

AU - Gustafsson, Jan-Ake

AU - Dahlman-Wright, Karin

N1 - Keywords: Algorithms; Animals; Base Sequence; Binding Sites; Chromatin; Chromatin Immunoprecipitation; DNA; Estradiol; Estrogen Receptor alpha; Female; Gene Expression Regulation; Genome; Liver; Mice; Mice, Inbred C57BL; Oligonucleotide Array Sequence Analysis; Polymerase Chain Reaction; Protein Binding; Pyrazoles

PY - 2007

Y1 - 2007

N2 - We report the genome-wide identification of estrogen receptor alpha (ERalpha)-binding regions in mouse liver using a combination of chromatin immunoprecipitation and tiled microarrays that cover all nonrepetitive sequences in the mouse genome. This analysis identified 5568 ERalpha-binding regions. In agreement with what has previously been reported for human cell lines, many ERalpha-binding regions are located far away from transcription start sites; approximately 40% of ERalpha-binding regions are located within 10 kb of annotated transcription start sites. Almost 50% of ERalpha-binding regions overlap genes. The majority of ERalpha-binding regions lie in regions that are evolutionarily conserved between human and mouse. Motif-finding algorithms identified the estrogen response element, and variants thereof, together with binding sites for activator protein 1, basic-helix-loop-helix proteins, ETS proteins, and Forkhead proteins as the most common motifs present in identified ERalpha-binding regions. To correlate ERalpha binding to the promoter of specific genes, with changes in expression levels of the corresponding mRNAs, expression levels of selected mRNAs were assayed in livers 2, 4, and 6 h after treatment with ERalpha-selective agonist propyl pyrazole triol. Five of these eight selected genes, Shp, Stat3, Pdgds, Pck1, and Pdk4, all responded to propyl pyrazole triol after 4 h treatment. These results extend our previous studies using gene expression profiling to characterize estrogen signaling in mouse liver, by characterizing the first step in this signaling cascade, the binding of ERalpha to DNA in intact chromatin.

AB - We report the genome-wide identification of estrogen receptor alpha (ERalpha)-binding regions in mouse liver using a combination of chromatin immunoprecipitation and tiled microarrays that cover all nonrepetitive sequences in the mouse genome. This analysis identified 5568 ERalpha-binding regions. In agreement with what has previously been reported for human cell lines, many ERalpha-binding regions are located far away from transcription start sites; approximately 40% of ERalpha-binding regions are located within 10 kb of annotated transcription start sites. Almost 50% of ERalpha-binding regions overlap genes. The majority of ERalpha-binding regions lie in regions that are evolutionarily conserved between human and mouse. Motif-finding algorithms identified the estrogen response element, and variants thereof, together with binding sites for activator protein 1, basic-helix-loop-helix proteins, ETS proteins, and Forkhead proteins as the most common motifs present in identified ERalpha-binding regions. To correlate ERalpha binding to the promoter of specific genes, with changes in expression levels of the corresponding mRNAs, expression levels of selected mRNAs were assayed in livers 2, 4, and 6 h after treatment with ERalpha-selective agonist propyl pyrazole triol. Five of these eight selected genes, Shp, Stat3, Pdgds, Pck1, and Pdk4, all responded to propyl pyrazole triol after 4 h treatment. These results extend our previous studies using gene expression profiling to characterize estrogen signaling in mouse liver, by characterizing the first step in this signaling cascade, the binding of ERalpha to DNA in intact chromatin.

U2 - 10.1210/me.2007-0121

DO - 10.1210/me.2007-0121

M3 - Journal article

C2 - 17901129

VL - 22

SP - 10

EP - 22

JO - Molecular Endocrinology

JF - Molecular Endocrinology

SN - 0888-8809

IS - 1

ER -