The genomic activity signaling of nuclear estrogen receptors (ERs) can be inhibited by ER-α36. The classical pathway of estrogen signaling is ligand-activated ERs bind specifically to estrogen response elements (EREs) in the promoter of target genes. The ligand-dependent indirect genomic regulation of gene transcription includes interactions with other transcription factors (TF). In ligand-independent pathway, ERs can be stimulated by other signaling pathways, such as growth factor signaling which eliciting genomic effects in the absence of ligands. In this case, activated kinases phosphorylate ERs, it thereby activate them to dimerize, bind DNA and regulate genes. ER-α36 can suppress both estrogen-dependent and estrogen-independent transactivation functions which signaling through nuclear ERs like ER-α66 and ER-β.