CAT7 and cat7l Long Non-coding RNAs Tune Polycomb Repressive Complex 1 Function during Human and Zebrafish Development

CAT7 和 cat7l 长非编码 RNA 在人类和斑马鱼发育过程中调节多梳抑制复合物 1 的功能

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作者:Mridula K Ray, Ole Wiskow, Matthew J King, Nidha Ismail, Ayla Ergun, Yanqun Wang, Aaron J Plys, Christopher P Davis, Katie Kathrein, Ruslan Sadreyev, Mark L Borowsky, Kevin Eggan, Leonard Zon, Jenna L Galloway, Robert E Kingston

Abstract

The essential functions of polycomb repressive complex 1 (PRC1) in development and gene silencing are thought to involve long non-coding RNAs (lncRNAs), but few specific lncRNAs that guide PRC1 activity are known. We screened for lncRNAs, which co-precipitate with PRC1 from chromatin and found candidates that impact polycomb group protein (PcG)-regulated gene expression in vivo A novel lncRNA from this screen, CAT7, regulates expression and polycomb group binding at the MNX1 locus during early neuronal differentiation. CAT7 contains a unique tandem repeat domain that shares high sequence similarity to a non-syntenic zebrafish analog, cat7l Defects caused by interference of cat7l RNA during zebrafish embryogenesis were rescued by human CAT7 RNA, enhanced by interference of a PRC1 component, and suppressed by interference of a known PRC1 target gene, demonstrating cat7l genetically interacts with a PRC1. We propose a model whereby PRC1 acts in concert with specific lncRNAs and that CAT7/cat7l represents convergent lncRNAs that independently evolved to tune PRC1 repression at individual loci.

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