TY - JOUR
T1 - A cluster of noncoding RNAs activates the ESR1 locus during breast cancer adaptation
AU - Tomita, Saori
AU - Abdalla, Mohamed Osama Ali
AU - Fujiwara, Saori
AU - Matsumori, Haruka
AU - Maehara, Kazumitsu
AU - Ohkawa, Yasuyuki
AU - Iwase, Hirotaka
AU - Saitoh, Noriko
AU - Nakao, Mitsuyoshi
N1 - Funding Information:
We thank all the members of our laboratory for discussions and technical assistance, Takumi Takizawa (Gunma University), Hideyuki Tanabe (The Graduate University for Advanced Studies), Sui Huang (Northwestern University), Christian Lanctot (Charles University in Prague), Gary Felsenfeld, Takashi Ideue (Kumamoto University) and Masahiko Harata (Tohoku University) for valuable advice, and Sakura Aoki (CTC Laboratory Systems) and Takehiko Oka (World Fusion) for helping with the bioinfor-matic analyses of the sequencing data. This work was supported by grants from the Ministry of Education, Culture, Sports, Science and Technology of Japan and the Japan Science and Technology Agency (CREST; M.N. and N.S.).
Publisher Copyright:
© 2015 Macmillan Publishers Limited. All rights reserved.
PY - 2015/4/29
Y1 - 2015/4/29
N2 - Estrogen receptor-α (ER)-positive breast cancer cells undergo hormone-independent proliferation after deprivation of oestrogen, leading to endocrine therapy resistance. Up-regulation of the ER gene (ESR1) is critical for this process, but the underlying mechanisms remain unclear. Here we show that the combination of transcriptome and fluorescence in situ hybridization analyses revealed that oestrogen deprivation induced a cluster of noncoding RNAs that defined a large chromatin domain containing the ESR1 locus. We termed these RNAs as Eleanors (ESR1 locus enhancing and activating noncoding RNAs). Eleanors were present in ER-positive breast cancer tissues and localized at the transcriptionally active ESR1 locus to form RNA foci. Depletion of one Eleanor, upstream (u)-Eleanor, impaired cell growth and transcription of intragenic Eleanors and ESR1 mRNA, indicating that Eleanors cis-activate the ESR1 gene. Eleanor-mediated gene activation represents a new type of locus control mechanism and plays an essential role in the adaptation of breast cancer cells.
AB - Estrogen receptor-α (ER)-positive breast cancer cells undergo hormone-independent proliferation after deprivation of oestrogen, leading to endocrine therapy resistance. Up-regulation of the ER gene (ESR1) is critical for this process, but the underlying mechanisms remain unclear. Here we show that the combination of transcriptome and fluorescence in situ hybridization analyses revealed that oestrogen deprivation induced a cluster of noncoding RNAs that defined a large chromatin domain containing the ESR1 locus. We termed these RNAs as Eleanors (ESR1 locus enhancing and activating noncoding RNAs). Eleanors were present in ER-positive breast cancer tissues and localized at the transcriptionally active ESR1 locus to form RNA foci. Depletion of one Eleanor, upstream (u)-Eleanor, impaired cell growth and transcription of intragenic Eleanors and ESR1 mRNA, indicating that Eleanors cis-activate the ESR1 gene. Eleanor-mediated gene activation represents a new type of locus control mechanism and plays an essential role in the adaptation of breast cancer cells.
UR - http://www.scopus.com/inward/record.url?scp=84928963426&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84928963426&partnerID=8YFLogxK
U2 - 10.1038/ncomms7966
DO - 10.1038/ncomms7966
M3 - Article
C2 - 25923108
AN - SCOPUS:84928963426
VL - 6
JO - Nature Communications
JF - Nature Communications
SN - 2041-1723
M1 - 6966
ER -
