ncRNA- and Pc2 methylation-dependent gene relocation between nuclear structures mediates gene activation programs
Open accessAbstract
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.
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ncRNAs, due to their conspicuous amount and proportion in the transcriptome, play a central role in epigenetics with an incidence in all functional levels.
“Overall, ncRNAs, due to their conspicuous amount and proportion in the transcriptome, play a central role in epigenetics with an incidence in all functional levels (Figure 2).”
From Revisiting Epigenetics Fundamentals and Its Biomedical Implications (2024) · cites this paper as [81]
The Introduction (page unavailable) describes long ncRNAs as a large class of transcriptional units, and the Results and Discussion (pages unavailable) show that specific ncRNAs participate in chromatin regulation and gene-expression programs. The paper does not establish their proportion of the transcriptome or show that they act at all functional levels of epigenetics; its findings concern specific ncRNAs and mechanisms. (LLM, conf=0.85)
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Cites
Chromatin modifications and their function
Kouzarides, T. (2007) · Cell · doi:10.1016/j.cell.2007.02.005 · Cited by 10,883 · see citing works
Long non-coding RNAs: insights into functions
Mercer, T. R., Dinger, M. E., & Mattick, J. S. (2009) · Nature Reviews Genetics · doi:10.1038/nrg2521 · Cited by 5,654 · see citing works
Long Noncoding RNA as Modular Scaffold of Histone Modification Complexes
Tsai, M.-C., Manor, O., Wan, Y., Mosammaparast, N., Wang, J. K., Lan, F., Shi, Y., Segal, E., & Chang, H. Y. (2010) · Science · doi:10.1126/science.1192002 · Cited by 3,290 · see citing works
Khalil, A. M., Guttman, M., Huarte, M., Garber, M., Raj, A., Rivea Morales, D., Thomas, K., Presser, A., Bernstein, B. E., van Oudenaarden, A., et al. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0904715106 · Cited by 2,872 · see citing works
Regulation of chromatin structure by site-specific histone H3 methyltransferases
Rea, S., Eisenhaber, F., O'Carroll, D., Strahl, B. D., Sun, Z.-W., Schmid, M., Opravil, S., Mechtler, K., Ponting, C. P., Allis, C. D., et al. (2000) · Nature · doi:10.1038/35020506 · Cited by 2,845 · cited 7× · see citing works
“In vitro methylation assay was performed by incubating GST-Suv39h1 (wt, H320R or H324L mutant) with His-Pc2 in the presence of [3H]-SAM.”
InfluentialGhisletti, S., Huang, W., Ogawa, S., Pascual, G., Lin, M.-E., Willson, T. M., Rosenfeld, M. G., & Glass, C. K. (2007) · Molecular Cell · doi:10.1016/j.molcel.2006.11.022 · Cited by 561 · see citing works
Self-citationPHF8 mediates histone H4 lysine 20 demethylation events involved in cell cycle progression.
Liu, W., Tanasa, B., Tyurina, O. V., Zhou, T. Y., Gassmann, R., Liu, W. T., Ohgi, K. A., Benner, C., Garcia-Bassets, I., Aggarwal, A. K., et al. (2010) · Nature · doi:10.1038/nature09272 · Cited by 441 · see citing works
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Flagged first, then by citations
Research works printed but not linked: 45
- Aagaard L Laible G Selenko P Schmid M Dorn R Schotta G Kuhfittig S Wolf A Lebersorger A Singh PB 1999 Functional mammalian homologues of the Drosophila PEV-modifier Su(var)3-9 encode centromere-associated proteins which complex with the heterochromatin component M31 EMBO J 18 1923 1938 10202156 PMC1171278
- Ait-Si-Ali S Guasconi V Fritsch L Yahi H Sekhri R Naguibneva I Robin P Cabon F Polesskaya A Harel-Bellan A 2004 A Suv39h-dependent mechanism for silencing S-phase genes in differentiating but not in cycling cells EMBO J 23 605 615 14765126 PMC1271807
- Akhtar A Zink D Becker PB 2000 Chromodomains are protein-RNA interaction modules Nature 407 405 409 11014199
- Bagchi S Weinmann R Raychaudhuri P 1991 The retinoblastoma protein copurifies with E2F-I, an E1A-regulated inhibitor of the transcription factor E2F Cell 65 1063 1072 1828393
- Bernstein E Duncan EM Masui O Gil J Heard E Allis CD 2006 Mouse polycomb proteins bind differentially to methylated histone H3 and RNA and are enriched in facultative heterochromatin Mol Cell Biol 26 2560 2569 16537902 PMC1430336
- Bond CS Fox AH 2009 Paraspeckles: nuclear bodies built on long noncoding RNA J Cell Biol 186 637 644 19720872 PMC2742191
- Campanero MR Flemington EK 1997 Regulation of E2F through ubiquitin-proteasome-dependent degradation: stabilization by the pRB tumor suppressor protein Proc Natl Acad Sci U S A 94 2221 2226 9122175 PMC20068
- Chuikov S Kurash JK Wilson JR Xiao B Justin N Ivanov GS McKinney K Tempst P Prives C Gamblin SJ 2004 Regulation of p53 activity through lysine methylation Nature 432 353 360 15525938
- Clemson CM Hutchinson JN Sara SA Ensminger AW Fox AH Chess A Lawrence JB 2009 An architectural role for a nuclear noncoding RNA: NEAT1 RNA is essential for the structure of paraspeckles Mol Cell 33 717 726 19217333 PMC2696186
- Cloos PA Christensen J Agger K Maiolica A Rappsilber J Antal T Hansen KH Helin K 2006 The putative oncogene GASC1 demethylates tri- and dimethylated lysine 9 on histone H3 Nature 442 307 311 16732293
- Czvitkovich S Sauer S Peters AH Deiner E Wolf A Laible G Opravil S Beug H Jenuwein T 2001 Over-expression of the SUV39H1 histone methyltransferase induces altered proliferation and differentiation in transgenic mice Mech Dev 107 141 153 11520670
- de la Luna S Burden MJ Lee CW La Thangue NB 1996 Nuclear accumulation of the E2F heterodimer regulated by subunit composition and alternative splicing of a nuclear localization signal J Cell Sci 109 Pt 10 2443 2452 8923205
- Deshaies RJ Joazeiro CA 2009 RING domain E3 ubiquitin ligases Annu Rev Biochem 78 399 434 19489725
- Eddy SR 2001 Non-coding RNA genes and the modern RNA world Nat Rev Genet 2 919 929 11733745
- Fodor BD Kubicek S Yonezawa M O’Sullivan RJ Sengupta R Perez-Burgos L Opravil S Mechtler K Schotta G Jenuwein T 2006 Jmjd2b antagonizes H3K9 trimethylation at pericentric heterochromatin in mammalian cells Genes Dev 20 1557 1562 16738407 PMC1482475
- Fu XD Maniatis T 1990 Factor required for mammalian spliceosome assembly is localized to discrete regions in the nucleus Nature 343 437 441 2137203
- Hernandez-Munoz I Taghavi P Kuijl C Neefjes J van Lohuizen M 2005 Association of BMI1 with polycomb bodies is dynamic and requires PRC2/EZH2 and the maintenance DNA methyltransferase DNMT1 Mol Cell Biol 25 11047 11058 16314526 PMC1316945
- Hu Q Kwon YS Nunez E Cardamone MD Hutt KR Ohgi KA Garcia-Bassets I Rose DW Glass CK Rosenfeld MG 2008 Enhancing nuclear receptor-induced transcription requires nuclear motor and LSD1-dependent gene networking in interchromatin granules Proc Natl Acad Sci U S A 105 19199 19204 19052240 PMC2593616
- Huang A Ho CS Ponzielli R Barsyte-Lovejoy D Bouffet E Picard D Hawkins CE Penn LZ 2005 Identification of a novel c-Myc protein interactor, JPO2, with transforming activity in medulloblastoma cells Cancer Res 65 5607 5619 15994933
- Huang J Berger SL 2008 The emerging field of dynamic lysine methylation of non-histone proteins Curr Opin Genet Dev 18 152 158 18339539
- Huang W Ghisletti S Saijo K Gandhi M Aouadi M Tesz GJ Zhang DX Yao J Czech MP Goode BL 2011 Coronin 2A mediates actin-dependent de-repression of inflammatory response genes Nature 470 414 418 21331046 PMC3464905
- Hutchinson JN Ensminger AW Clemson CM Lynch CR Lawrence JB Chess A 2007 A screen for nuclear transcripts identifies two linked noncoding RNAs associated with SC35 splicing domains BMC Genomics 8 39 17270048 PMC1800850
- Jenuwein T Allis CD 2001 Translating the histone code Science 293 1074 1080 11498575
- Kerscher O 2007 SUMO junction-what’s your function? New insights through SUMO-interacting motifs EMBO Rep 8 550 555 17545995 PMC2002525
- Lachner M O’Carroll D Rea S Mechtler K Jenuwein T 2001 Methylation of histone H3 lysine 9 creates a binding site for HP1 proteins Nature 410 116 120 11242053
- Lavrov S Dejardin J Cavalli G 2004 Combined immunostaining and FISH analysis of polytene chromosomes Methods Mol Biol 247 289 303 14707354
- Lund AH van Lohuizen M 2004 Polycomb complexes and silencing mechanisms Curr Opin Cell Biol 16 239 246 15145347
- Minsky N Shema E Field Y Schuster M Segal E Oren M 2008 Monoubiquitinated H2B is associated with the transcribed region of highly expressed genes in human cells Nat Cell Biol 10 483 488 18344985
- Misteli T 2010 Higher-order genome organization in human disease Cold Spring Harb Perspect Biol 2 a000794 20591991 PMC2908770
- Nahle Z Polakoff J Davuluri RV McCurrach ME Jacobson MD Narita M Zhang MQ Lazebnik Y Bar-Sagi D Lowe SW 2002 Direct coupling of the cell cycle and cell death machinery by E2F Nat Cell Biol 4 859 864 12389032
- Nevins JR 1992 Transcriptional regulation. A closer look at E2F Nature 358 375 376 1641018
- Nielsen SJ Schneider R Bauer UM Bannister AJ Morrison A O’Carroll D Firestein R Cleary M Jenuwein T Herrera RE 2001 Rb targets histone H3 methylation and HP1 to promoters Nature 412 561 565 11484059
- Peters AH O’Carroll D Scherthan H Mechtler K Sauer S Schofer C Weipoltshammer K Pagani M Lachner M Kohlmaier A 2001 Loss of the Suv39h histone methyltransferases impairs mammalian heterochromatin and genome stability Cell 107 323 337 11701123
- Ponting CP Oliver PL Reik W 2009 Evolution and functions of long noncoding RNAs Cell 136 629 641 19239885
- Qi HH Sarkissian M Hu GQ Wang Z Bhattacharjee A Gordon DB Gonzales M Lan F Ongusaha PP Huarte M 2010 Histone H4K20/H3K9 demethylase PHF8 regulates zebrafish brain and craniofacial development Nature 466 503 507 20622853 PMC3072215
- Sampath SC Marazzi I Yap KL Krutchinsky AN Mecklenbrauker I Viale A Rudensky E Zhou MM Chait BT Tarakhovsky A 2007 Methylation of a histone mimic within the histone methyltransferase G9a regulates protein complex assembly Mol Cell 27 596 608 17707231
- Satijn DP Olson DJ van der Vlag J Hamer KM Lambrechts C Masselink H Gunster MJ Sewalt RG van Driel R Otte AP 1997 Interference with the expression of a novel human polycomb protein, hPc2, results in cellular transformation and apoptosis Mol Cell Biol 17 6076 6086 9315667 PMC232457
- Sewalt RG Lachner M Vargas M Hamer KM den Blaauwen JL Hendrix T Melcher M Schweizer D Jenuwein T Otte AP 2002 Selective interactions between vertebrate polycomb homologs and the SUV39H1 histone lysine methyltransferase suggest that histone H3-K9 methylation contributes to chromosomal targeting of Polycomb group proteins Mol Cell Biol 22 5539 5553 12101246 PMC133945
- Simon JA Kingston RE 2009 Mechanisms of polycomb gene silencing: knowns and unknowns Nat Rev Mol Cell Biol 10 697 708 19738629
- Subramanian K Jia D Kapoor-Vazirani P Powell DR Collins RE Sharma D Peng J Cheng X Vertino PM 2008 Regulation of estrogen receptor alpha by the SET7 lysine methyltransferase Mol Cell 30 336 347 18471979 PMC2567917
- Szczerbal I Bridger JM 2010 Association of adipogenic genes with SC-35 domains during porcine adipogenesis Chromosome Res 18 887 895 21127962
- Ule J Jensen K Mele A Darnell RB 2005 CLIP: a method for identifying protein-RNA interaction sites in living cells Methods 37 376 386 16314267
- Wilusz JE Sunwoo H Spector DL 2009 Long noncoding RNAs: functional surprises from the RNA world Genes Dev 23 1494 1504 19571179 PMC3152381
- Xu X Hoang S Mayo MW Bekiranov S 2010 Application of machine learning methods to histone methylation ChIP-Seq data reveals H4R3me2 globally represses gene expression BMC Bioinformatics 11 396 20653935 PMC2928206
- Yamane K Toumazou C Tsukada Y Erdjument-Bromage H Tempst P Wong J Zhang Y 2006 JHDM2A, a JmjC-containing H3K9 demethylase, facilitates transcription activation by androgen receptor Cell 125 483 495 16603237
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- Authors
- Yang, L., Lin, C., Liu, W., Zhang, J., Ohgi, K. A., Grinstein, J. D., Dorrestein, P. C., & Rosenfeld, M. G.
- Affiliations
- Howard Hughes Medical Institute (US)
- University of California San Diego (US)
- Corresponding author
- Rosenfeld, Michael G.
- ORCID
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2011-11
- Volume
- 147
- Issue
- 4
- Pages
- 773-788
- ISSN
- 0092-8674 (ISSN-L)
- PMC
- PMC3297197
- OpenAlex
- W2169416332
- Cited by
- 612
- References
- 7
- Citations by year
- 2026: 7 · 2025: 13 · 2024: 16 · 2023: 22 · 2022: 25 · 2021: 35 · 2020: 46 · 2019: 50 · 2018: 44 · 2017: 56 · 2016: 59 · 2015: 67 · 2014: 73 · 2013: 56 · 2012: 40
- FWCI
- 18.61
- Type
- journal article
- Language
- en
- Update notices
- erratum (2013-10-10)
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (vor, 624 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- U.S. Department of Defense
- Howard Hughes Medical Institute
- Prostate Cancer Foundation
- Susan G. Komen
- National Heart, Lung, and Blood Institute (R01HL065445)
- National Cancer Institute (R01CA097134, CA97134)
- National Institute of Diabetes and Digestive and Kidney Diseases (DK39949, R01DK039949, DK018477, P01DK074868, R37DK039949, DK74868, R01DK018477)
- National Institute of Neurological Disorders and Stroke (R01NS034934, NS 34934)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer-related molecular mechanisms research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Keywords
- non-coding RNA, DNA methylation, interchromatin granules, nuclear organization, TUG1, MALAT1, gene activation, histone code, transcriptional regulation
- MeSH terms
- Amino Acid Sequence, Cell Line, Cell Nucleus, Chromatin, Gene Expression Regulation, HeLa Cells, Humans, Ligases, Methylation, Methyltransferases, Molecular Sequence Data, Repressor Proteins, Transcription, Genetic, RNA, Untranslated, Ubiquitin-Protein Ligases, E2F1 Transcription Factor, Ubiquitination, Sumoylation, RNA, Long Noncoding, Polycomb-Group Proteins
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