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The long non‐coding RNA Paupar promotes KAP 1‐dependent chromatin changes and regulates olfactory bulb neurogenesis
Author(s) -
Pavlaki Ioanna,
Alammari Farah,
Sun Bin,
Clark Neil,
Sirey Tamara,
Lee Sheena,
Woodcock Dan J,
Ponting Chris P,
Szele Francis G,
Vance Keith W
Publication year - 2018
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.201798219
Subject(s) - biology , neurogenesis , olfactory bulb , chromatin , microbiology and biotechnology , rna , long non coding rna , neuroscience , genetics , central nervous system , dna , gene
Many long non‐coding RNA s (lnc RNA s) are expressed during central nervous system ( CNS ) development, yet their in vivo roles and mechanisms of action remain poorly understood. Paupar , a CNS ‐expressed lnc RNA , controls neuroblastoma cell growth by binding and modulating the activity of transcriptional regulatory elements in a genome‐wide manner. We show here that the Paupar lnc RNA directly binds KAP 1, an essential epigenetic regulatory protein, and thereby regulates the expression of shared target genes important for proliferation and neuronal differentiation. Paupar promotes KAP 1 chromatin occupancy and H3K9me3 deposition at a subset of distal targets, through the formation of a ribonucleoprotein complex containing Paupar , KAP 1 and the PAX 6 transcription factor. Paupar ‐ KAP 1 genome‐wide co‐occupancy reveals a fourfold enrichment of overlap between Paupar and KAP 1 bound sequences, the majority of which also appear to associate with PAX 6. Furthermore, both Paupar and Kap1 loss‐of‐function in vivo disrupt olfactory bulb neurogenesis. These observations provide important conceptual insights into the trans ‐acting modes of lnc RNA ‐mediated epigenetic regulation and the mechanisms of KAP 1 genomic recruitment, and identify Paupar and Kap1 as regulators of neurogenesis in vivo .