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J Biol Chem. 2016 Sep 9;291(37):19558-72. doi: 10.1074/jbc.M116.730853. Epub 2016 Jul 12.

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

Author information

1
From the Department of Molecular Biology, Massachusetts General Hospital, and Department of Genetics, Harvard Medical School, Boston, Massachusetts 02114.
2
Harvard Stem Cell Institute, Department of Stem Cell and Regenerative Biology, Harvard University and the Stanley Center for Psychiatric Research, Broad Institute, Cambridge, Massachusetts 02138.
3
Center for Regenerative Medicine, Department of Orthopaedic Surgery, Massachusetts General Hospital, Harvard Stem Cell Institute, Harvard Medical School, Boston, Massachusetts 02114.
4
Department of Molecular Biology, Massachusetts General Hospital, and Department of Pathology, Harvard Medical School, Boston, Massachusetts 02114.
5
Division of Hematology/Oncology, Boston Children's Hospital, Dana-Farber Cancer Institute, Harvard Stem Cell Institute, Boston, Massachusetts, 02115, and.
6
Harvard Stem Cell Institute, Department of Stem Cell and Regenerative Biology, Harvard University and the Stanley Center for Psychiatric Research, Broad Institute, Cambridge, Massachusetts 02138, The Howard Hughes Medical Institute, Cambridge, MA 02138.
7
Center for Regenerative Medicine, Department of Orthopaedic Surgery, Massachusetts General Hospital, Harvard Stem Cell Institute, Harvard Medical School, Boston, Massachusetts 02114, jenna_galloway@hms.harvard.edu.
8
From the Department of Molecular Biology, Massachusetts General Hospital, and Department of Genetics, Harvard Medical School, Boston, Massachusetts 02114, kingston@molbio.mgh.harvard.edu.

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.

KEYWORDS:

CsCl density gradient; PRC1; chromatin; chromatin regulation; development; gene expression; long noncoding RNA (long ncRNA, lncRNA); mammal; polycomb; zebrafish

PMID:
27405765
PMCID:
PMC5016691
DOI:
10.1074/jbc.M116.730853
[Indexed for MEDLINE]
Free PMC Article

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