Nuclear role for human Argonaute-1 as an estrogen-dependent transcription coactivator

RODRÍGUEZ-SEGUÍ, SANTIAGO A.; MARASCO, LUCIANO E.; ALLÓ, MARIANO; NAZER, EZEQUIEL; BUGGIANO, VALERIA; HE, CODY; GÓMEZ ACUÑA, LUCIANA I.; POZZI, BERTA; AGIRRE, ENERITZ; KORNBLIHTT, ALBERTO R.

JOURNAL OF CELL BIOLOGY

ROCKEFELLER UNIV PRESS

Lugar: New York; Año: 2020 vol. 219 p. 1 - 14

0021-9525

In mammals, argonaute (AGO) proteins have been characterized for theirroles in small RNA?mediated posttranscriptional and also intranscriptional gene silencing. Here, we report a different role forAGO1 in estradiol-triggered transcriptional activation in human cells.We show that in MCF-7 mammary gland cells, AGO1 associates withtranscriptional enhancers of estrogen receptor α (ERα) and that thisassociation is up-regulated by treating the cells with estrogen (E2),displaying a positive correlation with the activation of theseenhancers. Moreover, we show that AGO1 interacts with ERα and that thisinteraction is also increased by E2 treatment, but occurs in the absenceof RNA. We show that AGO1 acts positively as a coactivator inestradiol-triggered transcription regulation by promoting ERα binding toits enhancers. Consistently, AGO1 depletion decreases long-rangecontacts between ERα enhancers and their target promoters. Our resultspoint to a role of AGO1 in transcriptional regulation in human cellsthat is independent from small RNA binding.