@article{5f84326e76a4452093d2becbb5832036,
title = "Estrogen-induced transcription at individual alleles is independent of receptor level and active conformation but can be modulated by coactivators activity",
abstract = "Steroid hormones are pivotal modulators of pathophysiological processes in many organs, where they interact with nuclear receptors to regulate gene transcription. However, our understanding of hormone action at the single cell level remains incomplete. Here, we focused on estrogen stimulation of the well-characterized GREB1 and MYC target genes that revealed large differences in cell-by-cell responses, and, more interestingly, between alleles within the same cell, both over time and hormone concentration. We specifically analyzed the role of receptor level and activity state during allele-by-allele regulation and found that neither receptor level nor activation status are the determinant of maximal hormonal response, indicating that additional pathways are potentially in place to modulate cell- and allele-specific responses. Interestingly, we found that a small molecule inhibitor of the arginine methyltransferases CARM1 and PRMT6 was able to increase, in a gene specific manner, the number of active alleles/cell before and after hormonal stimulation, suggesting that mechanisms do indeed exist to modulate hormone receptor responses at the single cell and allele level.",
author = "Fabio Stossi and Dandekar, {Radhika D.} and Mancini, {Maureen G.} and Guowei Gu and Fuqua, {Suzanne A.W.} and Agostina Nardone and {De Angelis}, Carmine and Xiaoyong Fu and Rachel Schiff and Bedford, {Mark T.} and Wei Xu and Johansson, {Hans E.} and Stephan, {Clifford C.} and Mancini, {Michael A.}",
note = "Funding Information: M.A.M. is supported by an NIH/NIEHS Superfund grant [P42ES027704]; M.A.M. and F.S. are supported via the CPRIT-funded GCC Center for Advanced Microscopy and Image Informatics [RP170719]; M.T.B. is supported by NIH [GM126421]; S.A.W.F. by NIH [R01-CA72038]; CPRIT [RP120732]; Breast Cancer Research Foundation; R.S. by the Breast Cancer Research Foundation, NIH Breast Cancer Specialized Programs of Research Excellence Grants [P50CA058183, P50CA186784]; S.G.K. for the Cure Foundation Promise Grant [PG12221410]; Imaging was supported by the Integrated Microscopy Core at Baylor College of Medicine with funding from NIH [DK56338, CA125123]; CPRIT [RP150578]; Dan L. Duncan Comprehensive Cancer Center, and the John S. Dunn Gulf Coast Consortium for Chemical Genomics; The Gulf Coast Consortium for Chemical Genomics high throughput screening center is funded by CPRIT [RP110532, RP150578]. Funding for open access charge: CPRIT [RP170719]. Conflict of interest statement. Hans E. Johansson is an employee of LGC Biosearch Technologies. Publisher Copyright: {\textcopyright} 2020 The Author(s) 2020. Published by Oxford University Press on behalf of Nucleic Acids Research.",
year = "2020",
month = feb,
day = "28",
doi = "10.1093/nar/gkz1172",
language = "English (US)",
volume = "48",
pages = "1800--1810",
journal = "Nucleic acids research",
issn = "0305-1048",
publisher = "Oxford University Press",
number = "4",
}