Histone H2A.Z is essential for estrogen receptor signaling.
Incorporation of H2A.Z into the chromatin of inactive promoters has been shown to poise genes for their expression. Here we provide strong evidence that H2A.Z is incorporated into the promoter regions of estrogen receptor (ERalpha) target genes only upon gene induction, and that, in a cyclic pattern. Moreover, members of the human H2A.Z-depositing complex, p400, also follow the same gene recruitment kinetics as H2A.Z. Importantly, cellular depletion of H2A.Z or p400 leads to a severe defect in estrogen signaling, including loss of estrogen-specific cell proliferation. We find that incorporation of H2A.Z within TFF1 promoter chromatin allows nucleosomes to adopt preferential positions along the DNA translational axis. Finally, we provide evidence that H2A.Z is essential to allow estrogen-responsive enhancer function. Taken together, our results provide strong mechanistic insight into how H2A.Z regulates ERalpha-mediated gene expression and provide a novel link between H2A.Z-p400 and ERalpha-dependent gene regulation and enhancer function.
Gévry
Nicolas
N
Département de biologie, Faculté des sciences, Université de Sherbrooke, Sherbrooke, Québec, Canada.
Hardy
Sara
S
Jacques
Pierre-Etienne
PE
Laflamme
Liette
L
Svotelis
Amy
A
Robert
François
F
Gaudreau
Luc
L
D000251:Adenosine Triphosphatases / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002843:Chromatin / Q000378:metabolism; D004967:Estrogens / Q000502:physiology; D005786:Gene Expression Regulation; D051541:Hepatocyte Nuclear Factor 3-alpha / Q000378:metabolism; D006657:Histones / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008024:Ligands; D009707:Nucleosomes / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000235:genetics*; D011960:Receptors, Estrogen / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction; D000071163:Trefoil Factor-1; D025521:Tumor Suppressor Proteins / Q000235:genetics
D002843:Chromatin; D004967:Estrogens; C496499:FOXA1 protein, human; C468783:H2AX protein, human; D051541:Hepatocyte Nuclear Factor 3-alpha; D006657:Histones; D008024:Ligands; D009707:Nucleosomes; D011960:Receptors, Estrogen; C051838:TFF1 protein, human; D000071163:Trefoil Factor-1; D025521:Tumor Suppressor Proteins; C077020:histone H2A.F-Z; D000251:Adenosine Triphosphatases; C119652:SRCAP protein, human