title: ncRNA- and Pc2 methylation-dependent gene relocation between nuclear structures mediates gene activation programs.
abstract: Although eukaryotic nuclei contain distinct architectural structures associated with noncoding RNAs (ncRNAs), their potential relationship to regulated transcriptional programs remains poorly understood. Here, we report that methylation/demethylation of Polycomb 2 protein (Pc2) controls relocation of growth-control genes between Polycomb bodies (PcGs) and interchromatin granules (ICGs) in response to growth signals. This movement is the consequence of binding of methylated and unmethylated Pc2 to the ncRNAs TUG1 and MALAT1/NEAT2, located in PcGs and ICGs, respectively. These ncRNAs mediate assembly of multiple corepressors/coactivators and can serve to switch mark recognition by "readers" of the histone code. Additionally, binding of NEAT2 to unmethylated Pc2 promotes E2F1 SUMOylation, leading to activation of the growth-control gene program. These observations delineate a molecular pathway linking the actions of subnuclear structure-specific ncRNAs and nonhistone protein methylation to relocation of transcription units in the three-dimensional space of the nucleus, thus achieving coordinated gene expression programs.
authors.affiliation: Howard Hughes Medical Institute, University of California, San Diego, School of Medicine, 9500 Gilman Drive, La Jolla, CA 92093-0648, USA.
authors.forename: Liuqing
authors.initials: L
authors.lastname: Yang
authors.forename: Chunru
authors.initials: C
authors.lastname: Lin
authors.forename: Wen
authors.initials: W
authors.lastname: Liu
authors.forename: Jie
authors.initials: J
authors.lastname: Zhang
authors.forename: Kenneth A
authors.initials: KA
authors.lastname: Ohgi
authors.forename: Jonathan D
authors.initials: JD
authors.lastname: Grinstein
authors.forename: Pieter C
authors.initials: PC
authors.lastname: Dorrestein
authors.forename: Michael G
authors.initials: MG
authors.lastname: Rosenfeld
mesh_terms: D000595:Amino Acid Sequence; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism*; D002843:Chromatin / Q000378:metabolism; D050687:E2F1 Transcription Factor / Q000378:metabolism; D005786:Gene Expression Regulation; D006367:HeLa Cells; D006801:Humans; D008025:Ligases; D008745:Methylation; D008780:Methyltransferases / Q000378:metabolism; D008969:Molecular Sequence Data; D063146:Polycomb-Group Proteins; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated / Q000378:metabolism*; D012097:Repressor Proteins / Q000737:chemistry / Q000378:metabolism*; D058207:Sumoylation; D014158:Transcription, Genetic; D044767:Ubiquitin-Protein Ligases; D054875:Ubiquitination
chemical_list: C513450:CDCA7L protein, human; D002843:Chromatin; D050687:E2F1 Transcription Factor; C493753:E2F1 protein, human; C557041:MALAT1 long non-coding RNA, human; D063146:Polycomb-Group Proteins; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated; D012097:Repressor Proteins; C407843:SUV39H1 protein, human; D008780:Methyltransferases; D044767:Ubiquitin-Protein Ligases; D008025:Ligases; C570427:CBX4 protein, human
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