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Divergent lnc RNA MYMLR regulates MYC by eliciting DNA looping and promoter‐enhancer interaction
Author(s) -
Kajino Taisuke,
Shimamura Teppei,
Gong Shuyi,
Yanagisawa Kiyoshi,
Ida Lisa,
Nakatochi Masahiro,
Griesing Sebastian,
Shimada Yukako,
Kano Keiko,
Suzuki Motoshi,
Miyano Satoru,
Takahashi Takashi
Publication year - 2019
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.15252/embj.201798441
Subject(s) - biology , enhancer , dna , rna , dna binding protein , microbiology and biotechnology , genetics , gene , transcription factor
Long non‐coding RNA s (lnc RNA s) function in a wide range of processes by diverse mechanisms, though their roles in regulation of oncogenes and/or tumor suppressors remain rather elusive. We performed a global search for lnc RNA s affecting MYC activity using a systems biology‐based approach with a K supercomputer and the GIMLET algorism based on local distance correlations. Consequently, MYMLR was identified and experimentally shown to maintain MYC transcriptional activity and cell cycle progression despite the low levels of expression. A proteomic search for MYMLR ‐binding proteins identified PCBP 2, while it was also found that MYMLR places a 557‐kb upstream enhancer region in the proximity of the MYC promoter in cooperation with PCBP 2. These findings implicate a crucial role for MYMLR in regulation of the archetypical oncogene MYC and warrant future studies regarding the involvement of low copy number lnc RNA s in regulation of other crucial oncogenes and tumor suppressor genes.