Abstract
In the nucleus, genomic DNA is wrapped around histone octamers to form nucleosomes. In principle, nucleosomes are substantial barriers to transcriptional activities. Nuclear non-coding RNAs (ncRNAs) are proposed to function in chromatin conformation modulation and transcriptional regulation. However, it remains unclear how ncRNAs affect the nucleosome structure. Eleanors are clusters of ncRNAs that accumulate around the estrogen receptor-α (ESR1) gene locus in long-term estrogen deprivation (LTED) breast cancer cells, and markedly enhance the transcription of the ESR1 gene. Here we detected nucleosome depletion around the transcription site of Eleanor2, the most highly expressed Eleanor in the LTED cells. We found that the purified Eleanor2 RNA fragment drastically destabilized the nucleosome in vitro. This activity was also exerted by other ncRNAs, but not by poly(U) RNA or DNA. The RNA-mediated nucleosome destabilization may be a common feature among natural nuclear RNAs, and may function in transcription regulation in chromatin.
Highlights
In the nucleus, genomic DNA is wrapped around histone octamers to form nucleosomes
We previously reported that a cluster of noncoding RNAs (ncRNAs), named Eleanors, is transcribed from a 0.7-Mb region containing the ESR1 gene in long-term estrogen deprivation (LTED) cells derived from human breast cancer MCF7 cells[25]
The formaldehyde-assisted isolation of regulatory elements (FAIRE)-seq data (Fig. 1a, b) revealed that nucleosomes may be destabilized in the region upstream of the ESR1 gene in LTED cells, but not in MCF10A, non-tumorigenic mammary epithelial cells
Summary
Genomic DNA is wrapped around histone octamers to form nucleosomes. In principle, nucleosomes are substantial barriers to transcriptional activities. Nuclear noncoding RNAs (ncRNAs) are proposed to function in chromatin conformation modulation and transcriptional regulation. It remains unclear how ncRNAs affect the nucleosome structure. Eleanors are clusters of ncRNAs that accumulate around the estrogen receptor-α (ESR1) gene locus in long-term estrogen deprivation (LTED) breast cancer cells, and markedly enhance the transcription of the ESR1 gene. We found that the purified Eleanor[2] RNA fragment drastically destabilized the nucleosome in vitro This activity was exerted by other ncRNAs, but not by poly(U) RNA or DNA. A cluster of ncRNAs named Eleanors (ESR1 locus enhancing and activating noncoding RNAs) is highly transcribed from a 0.7-Mb genomic region, including the ESR1 gene, on human chromosome 6. These novel intrinsic properties of ncRNAs may explain the higher chromatin accessibility, by which Eleanor[2] accumulates and activates the nearby gene, ESR1
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
