PT - JOURNAL ARTICLE AU - Ricardo Saldaña-Meyer AU - Javier Rodriguez-Hernaez AU - Mayilaadumveettil Nishana AU - Karina Jácome-López AU - Elphege P. Nora AU - Benoit G. Bruneau AU - Mayra Furlan-Magaril AU - Jane Skok AU - Danny Reinberg TI - RNA interactions with CTCF are essential for its proper function AID - 10.1101/530014 DP - 2019 Jan 01 TA - bioRxiv PG - 530014 4099 - http://biorxiv.org/content/early/2019/01/24/530014.short 4100 - http://biorxiv.org/content/early/2019/01/24/530014.full AB - The function of the CCCTC-binding factor (CTCF) in the organization of the genome has become an important area of investigation, but the mechanisms of how CTCF dynamically contributes to genome organization is not clear. We previously discovered that CTCF binds to large numbers of endogenous RNAs; promoting its oligomerization. Here we found that inhibition of transcription or interfering with CTCF ability to bind RNA through mutations of two of its 11 zinc fingers that are not involved with CTCF binding to its cognate site in vitro, zinc finger-1 (ZF1) or −10 (ZF10), disrupt CTCF association to chromatin. These mutations alter gene expression profiles as CTCF mutants lose their ability to promote local insulation. Our results highlight the importance of RNA as a structural component of the genome, in part by affecting the association of CTCF with chromatin and likely its interaction with other factors.Transcriptional inhibition disrupts CTCF binding to chromatinRNA-binding regions (RBR) in CTCF are found within ZF1 and ZF10Local insulation is markedly decreased in ZF1∆ and ZF10∆ mutant rescuesGene expression and chromatin organization are disrupted by RBR mutants