ncRNA- and Pc2 Methylation-Dependent Gene Relocation between Nuclear Structures Mediates Gene Activation Programs

By Liuqing Yang, Chunru Lin, Wen Liu, Jie Zhang, K. Ohgi, Jonathan D. Grinstein, Pieter C. Dorrestein, Michael G. Rosenfeld. Cell, 2011

623 citations recorded by the source corpus.

Summary 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 co-repressors/co-activators, and can alter the histone marks read by Pc2 in vitro. 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 non-histone protein methylation to relocation of transcription units in the three-dimensional space of the nucleus, thus achieving coordinated gene expression programs.

Subfields: Molecular Biology

View Paper: https://www.semanticscholar.org/paper/841b2a1a80bf48c76126d4599e9c14a02ee72edb

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Citations in the corpus

The noncoding RNA MALAT1 is a critical regulator of the metastasis phenotype of lung cancer cells. (2013, background): “Alternative splicing is not affected by loss of MALAT1 MALAT1 had been previously linked to two different molecular mechanisms: regulating alternative splicing (22) and regulating gene expression (25).”
Long Noncoding RNAs: Past, Present, and Future (2013, background): “…called interchromatin granules that usually cluster around nuclear speckles; in the absence of signal, Cbx4 becomes methylated and instead binds another lncRNA TUG1, associates with corepressors such as Ezh2, and translocates to silencing compartments called Polycomb bodies (L. Yang et al. 2011).”
Localization and abundance analysis of human lncRNAs at single-cell and single-molecule resolution (2015, result): “Validating our approach, 11 of the 12 lncRNA previously imaged by RNA FISH [6,19,21,25,49-56] showed patterns that were consistent with previous reports (Additional file 3).”