Heterochromatin organization and phase separation

References

• Dundr M, Misteli T. Functional architecture in the cell nucleus. Biochem J. 2001;356(2):297–13.
   PubMedGoogle Scholar
• Botchkarev VA, Gdula MR, Mardaryev AN, et al. Epigenetic regulation of gene expression in keratinocytes. J Invest Dermatol. 2012;132(11):2505–2521.
   PubMed Web of Science ®Google Scholar
• Grewal SIS, Moazed D. Heterochromatin and epigenetic control of gene expression. Science. 2003;301(5634):798–802.
   PubMed Web of Science ®Google Scholar
• Guillemette B, Drogaris P, Lin -H-HS, et al. H3 lysine 4 is acetylated at active gene promoters and is regulated by H3 lysine 4 methylation. PLoS Genet. 2011;7(3):e1001354.
   PubMed Web of Science ®Google Scholar
• Hennig WH. Chromosoma. Vol. 108. 1999. p. 1–9. Heterochromatin.
   PubMed Web of Science ®Google Scholar
• Allshire RC, Madhani HD. Ten principles of heterochromatin formation and function. Nat Rev Mol Cell Biol. 2018;19(4):229–244.
   PubMed Web of Science ®Google Scholar
• Poleshko A, Smith CL, Nguyen SC, et al. H3K9me2 orchestrates inheritance of spatial positioning of peripheral heterochromatin through mitosis. eLife. 2019;8:e49278.
   PubMed Web of Science ®Google Scholar
• Peters AH, O’Carroll D, Scherthan H, et al. Loss of the Suv39h histone methyltransferases impairs mammalian heterochromatin and genome stability. Cell. 2001;107(3):323–337.
   PubMed Web of Science ®Google Scholar
• Cheutin T, McNairn AJ, Jenuwein T, et al. Maintenance of stable heterochromatin domains by dynamic HP1 binding. Science. 2003;299(5607):721–725.
   PubMed Web of Science ®Google Scholar
• Simon SA, Meyers BC. Small RNA-mediated epigenetic modifications in plants. Curr Opin Plant Biol. 2011;14(2):148–155.
   PubMed Web of Science ®Google Scholar
• Yan S-J, Lim SJ, Shi S, et al. Unphosphorylated STAT and heterochromatin protect genome stability. FASEB J. 2011;25(1):232–241.
   PubMed Web of Science ®Google Scholar
• Johnson WL, Straight AF. RNA-mediated regulation of heterochromatin. Curr Opin Cell Biol. 2017;46:102–109.
   PubMed Web of Science ®Google Scholar
• Strom AR, Emelyanov AV, Mir M, et al. Phase separation drives heterochromatin domain formation. Nature. 2017;547(7662):241–245.
   PubMed Web of Science ®Google Scholar
• Isaac RS, Sanulli S, Tibble R, et al. Biochemical basis for distinct roles of the heterochromatin proteins swi6 and chp2. J Mol Biol. 2017;429(23):3666–3677.
   PubMed Web of Science ®Google Scholar
• Johnson WL, Yewdell WT, Bell JC, et al. RNA-dependent stabilization of SUV39H1 at constitutive heterochromatin. eLife. 2017;6:e25299.
   PubMed Web of Science ®Google Scholar
• Erdel F, Rademacher A, Vlijm R, et al. Mouse heterochromatin adopts digital compaction states without showing hallmarks of HP1-driven liquid-liquid phase separation. Mol Cell. 2020;78(2):236–249.e7.
   PubMed Web of Science ®Google Scholar
• Nava MM, Miroshnikova YA, Biggs LC, et al. Heterochromatin-driven nuclear softening protects the genome against mechanical stress-induced damage. Cell. 2020;181(4):800–817.e22.
   PubMed Web of Science ®Google Scholar
• Brero A, Easwaran HP, Nowak D, et al. Methyl CpG-binding proteins induce large-scale chromatin reorganization during terminal differentiation. J Cell Biol. 2005;169(5):733–743.
   PubMed Web of Science ®Google Scholar
• Janssen A, Colmenares SU, Karpen GH. Heterochromatin: guardian of the genome. Annu Rev Cell Dev Biol. 2018;34(1):265–288.
   PubMedGoogle Scholar
• Greenstein RA, Al-Sady B. Epigenetic fates of gene silencing established by heterochromatin spreading in cell identity and genome stability. Curr Genet. 2019;65(2):423–428.
   PubMed Web of Science ®Google Scholar
• Falk M, Feodorova Y, Naumova N, et al. Heterochromatin drives compartmentalization of inverted and conventional nuclei. Nature. 2019;570(7761):395–399.
   PubMed Web of Science ®Google Scholar
• Shah PP, Donahue G, Otte GL, et al. Lamin B1 depletion in senescent cells triggers large-scale changes in gene expression and the chromatin landscape. Genes Dev. 2013;27(16):1787–1799.
   PubMed Web of Science ®Google Scholar
• Chen H, Zheng X, Zheng Y. Age-associated loss of lamin-B leads to systemic inflammation and gut hyperplasia. Cell. 2014;159(4):829–843.
   PubMed Web of Science ®Google Scholar
• McCord RP, Nazario-Toole A, Zhang H, et al. Correlated alterations in genome organization, histone methylation, and DNA-lamin A/C interactions in Hutchinson-Gilford progeria syndrome. Genome Res. 2013;23(2):260–269.
   PubMed Web of Science ®Google Scholar
• Fernandez P, Scaffidi P, Markert E, et al. Transformation resistance in a premature aging disorder identifies a tumor-protective function of BRD4. Cell Rep. 2014;9(1):248–260.
   PubMed Web of Science ®Google Scholar
• Loi M, Cenni V, Duchi S, et al. Barrier-to-autointegration factor (BAF) involvement in prelamin A-related chromatin organization changes. Oncotarget. 2016;7(13):15662–15677.
   PubMedGoogle Scholar
• Koenhen DM, Mulder MHV, Smolders CA. Phase separation phenomena during the formation of asymmetric membranes. J Appl Polym Sci. 1977;21(1):199–215.
   Web of Science ®Google Scholar
• Muschol M, Rosenberger F. Liquid–liquid phase separation in supersaturated lysozyme solutions and associated precipitate formation/crystallization. J Chem Phys. 1997;107(6):1953–1962.
   Web of Science ®Google Scholar
• Brangwynne CP, Eckmann CR, Courson DS, et al. Germline P granules are liquid droplets that localize by controlled dissolution/condensation. Science. 2009;324(5935):1729–1732.
   PubMed Web of Science ®Google Scholar
• Oldfield CJ, Dunker AK. Intrinsically disordered proteins and intrinsically disordered protein regions. Annu Rev Biochem. 2014;83(1):553–584.
   PubMed Web of Science ®Google Scholar
• Habchi J, Tompa P, Longhi S, et al. Introducing protein intrinsic disorder. Chem Rev. 2014;114(13):6561–6588.
   PubMed Web of Science ®Google Scholar
• Wright PE, Dyson HJ. Intrinsically disordered proteins in cellular signalling and regulation. Nat Rev Mol Cell Biol. 2015;16(1):18–29.
   PubMed Web of Science ®Google Scholar
• Dyson HJ, Wright PE. Intrinsically unstructured proteins and their functions. Nat Rev Mol Cell Biol. 2005;6(3):197–208.
   PubMed Web of Science ®Google Scholar
• Dunker AK, Lawson JD, Brown CJ, et al. Intrinsically disordered protein. J Mol Graph Model. 2001;19(1):26–59.
   PubMed Web of Science ®Google Scholar
• Molliex A, Temirov J, Lee J, et al. Phase separation by low complexity domains promotes stress granule assembly and drives pathological fibrillization. Cell. 2015;163(1):123–133.
   PubMed Web of Science ®Google Scholar
• Brangwynne CP, Tompa P, Pappu RV. Polymer physics of intracellular phase transitions. Nat Phys. 2015;11(11):899–904.
   Web of Science ®Google Scholar
• Krainer G, Welsh TJ, Joseph JA, et al. Reentrant liquid condensate phase of proteins is stabilized by hydrophobic and non-ionic interactions. Nat Commun. 2021;12(1):1085.
   PubMed Web of Science ®Google Scholar
• Li P, Banjade S, Cheng H-C, et al. Phase transitions in the assembly of multivalent signalling proteins. Nature. 2012;483(7389):336–340.
   PubMed Web of Science ®Google Scholar
• Riback JA, Katanski CD, Kear-Scott JL, et al. Stress-triggered phase separation is an adaptive, evolutionarily tuned response. Cell. 2017;168(6):1028–1040.e19.
   PubMed Web of Science ®Google Scholar
• Lücking CB, Brice A. Alpha-synuclein and Parkinson’s disease. Cell Mol Life Sci. 2000;57(13):1894–1908.
   PubMed Web of Science ®Google Scholar
• Ray S, Singh N, Kumar R, et al. α-Synuclein aggregation nucleates through liquid-liquid phase separation. Nat Chem. 2020;12(8):705–716.
   PubMed Web of Science ®Google Scholar
• Kanaan NM, Hamel C, Grabinski T, et al. Liquid-liquid phase separation induces pathogenic tau conformations in vitro. Nat Commun. 2020;11(1):2809.
   PubMed Web of Science ®Google Scholar
• Strickfaden H, Tolsma TO, Sharma A, et al. Condensed chromatin behaves like a solid on the mesoscale in vitro and in living cells. Cell. 2020;183(7):1772–1784.e13.
   PubMed Web of Science ®Google Scholar
• Gibson BA, Doolittle LK, Schneider MWG, et al. Organization of chromatin by intrinsic and regulated phase separation. Cell. 2019;179(2):470–484.e21.
   PubMed Web of Science ®Google Scholar
• Becker A, Allmann L, Hofstätter M, et al. Direct homo- and hetero-interactions of MeCP2 and MBD2. PLoS ONE. 2013;8(1):e53730.
   PubMed Web of Science ®Google Scholar
• Larson AG, Narlikar GJ. The role of phase separation in heterochromatin formation, function, and regulation. Biochemistry. 2018;57(17):2540–2548.
   PubMed Web of Science ®Google Scholar
• Boija A, Klein IA, Sabari BR, et al. Transcription factors activate genes through the phase-separation capacity of their activation domains. Cell. 2018;175(7):1842–1855.e16.
   PubMed Web of Science ®Google Scholar
• Sabari BR, Dall’Agnese A, Boija A, et al. Coactivator condensation at super-enhancers links phase separation and gene control. Science. 2018;361(6400):eaar3958.
   PubMed Web of Science ®Google Scholar
• Parker MW, Bell M, Mir M, et al. A new class of disordered elements controls DNA replication through initiator self-assembly. eLife. 2019;8:e48562.
   PubMed Web of Science ®Google Scholar
• Wang L, Gao Y, Zheng X, et al. Histone modifications regulate chromatin compartmentalization by contributing to a phase separation mechanism. Mol Cell. 2019;76(4):646–659.e6.
   PubMed Web of Science ®Google Scholar
• Laflamme G, Mekhail K. Biomolecular condensates as arbiters of biochemical reactions inside the nucleus. Commun Biol. 2020;3(1):773.
   PubMed Web of Science ®Google Scholar
• Levone BR, Lenzken SC, Antonaci M, et al. FUS-dependent liquid-liquid phase separation is important for DNA repair initiation. J Cell Biol. 2021;220(5):e202008030.
   PubMed Web of Science ®Google Scholar
• Reber S, Jutzi D, Lindsay H, et al. The phase separation-dependent FUS interactome reveals nuclear and cytoplasmic function of liquid-liquid phase separation. Nucleic Acids Res. 2021;49(13):7713–7731.
   PubMed Web of Science ®Google Scholar
• Pessina F, Gioia U, Brandi O, et al. DNA damage triggers a new phase in neurodegeneration. Trends Genet. 2021;37(4):337–354.
   PubMed Web of Science ®Google Scholar
• Shi B, Li W, Song Y, et al. UTX condensation underlies its tumour-suppressive activity. Nature. 2021;597(7878):726–731.
   PubMed Web of Science ®Google Scholar
• Zhang L, Geng X, Wang F, et al. 53BP1 regulates heterochromatin through liquid phase separation. Nat Commun. 2022;13(1):360.
   PubMed Web of Science ®Google Scholar
• Wang L, Hu M, Zuo M-Q, et al. Rett syndrome-causing mutations compromise MeCP2-mediated liquid-liquid phase separation of chromatin. Cell Res. 2020;30(5):393–407.
   PubMed Web of Science ®Google Scholar
• Zhang H, Romero H, Schmidt A, et al. MeCP2-induced heterochromatin organization is driven by oligomerization-based liquid-liquid phase separation and restricted by DNA methylation. Nucleus. 2022;13(1):1–34.
   PubMed Web of Science ®Google Scholar
• Li CH, Coffey EL, Dall’Agnese A, et al. MeCP2 links heterochromatin condensates and neurodevelopmental disease. Nature. 2020;586(7829):440–444.
   PubMed Web of Science ®Google Scholar
• Huo X, Ji L, Zhang Y, et al. The nuclear matrix protein SAFB Cooperates with major satellite RNAs to stabilize heterochromatin architecture partially through phase separation. Mol Cell. 2020;77(2):368–383.e7.
   PubMed Web of Science ®Google Scholar
• Pandya-Jones A, Markaki Y, Serizay J, et al. A protein assembly mediates Xist localization and gene silencing. Nature. 2020;587(7832):145–151.
   PubMed Web of Science ®Google Scholar
• Jack A, Kim Y, Strom AR, et al. Compartmentalization of telomeres through DNA-scaffolded phase separation. Dev Cell. 2022;57(2):277–290.e9.
   PubMed Web of Science ®Google Scholar
• Qin W, Ugur E, Mulholland CB, et al. Phosphorylation of the HP1β hinge region sequesters KAP1 in heterochromatin and promotes the exit from naïve pluripotency. Nucleic Acids Res. 2021;49(13):7406–7423.
   PubMed Web of Science ®Google Scholar
• Qin W, Stengl A, Ugur E, et al. HP1β carries an acidic linker domain and requires H3K9me3 for phase separation. Nucleus. 2021;12(1):44–57.
   PubMed Web of Science ®Google Scholar
• Lyon MF. Gene action in the X-chromosome of the mouse (Mus musculus L.). Nature. 1961;190(4773):372–373.
   PubMedGoogle Scholar
• Yang F, Deng X, Ma W, et al. The lncRNA Firre anchors the inactive X chromosome to the nucleolus by binding CTCF and maintains H3K27me3 methylation. Genome Biol. 2015;16(1):52.
   PubMedGoogle Scholar
• Fang HE, Bonora G, Lewandowski J, et al. Trans− and cis−acting effects of Firre on epigenetic features of the inactive X chromosome. Nat Commun. 2020;11(1):6053.
   PubMed Web of Science ®Google Scholar
• Maduro C, de Hoon B, Gribnau J. Fitting the puzzle pieces: the bigger picture of XCI. Trends Biochem Sci. 2016;41(2):138–147.
   PubMed Web of Science ®Google Scholar
• Wutz A, Jaenisch R. A shift from reversible to irreversible X inactivation is triggered during ES cell differentiation. Mol Cell. 2000;5(4):695–705.
   PubMed Web of Science ®Google Scholar
• Coelho MB, Attig J, Ule J, et al. Matrin3: connecting gene expression with the nuclear matrix. Wiley Interdiscip Rev RNA. 2016;7(3):303–315.
   PubMed Web of Science ®Google Scholar
• Prasad A, Bharathi V, Sivalingam V, et al. Molecular mechanisms of TDP-43 misfolding and pathology in amyotrophic lateral sclerosis. Front Mol Neurosci. 2019;12:25.
   PubMed Web of Science ®Google Scholar
• McHugh CA, Chen C-K, Chow A, et al. The Xist lncRNA interacts directly with SHARP to silence transcription through HDAC3. Nature. 2015;521(7551):232–236.
   PubMed Web of Science ®Google Scholar
• Gallego-Iradi MC, Strunk H, Crown AM, et al. N-terminal sequences in matrin 3 mediate phase separation into droplet-like structures that recruit TDP43 variants lacking RNA binding elements. Lab Invest. 2019;99(7):1030–1040.
   PubMed Web of Science ®Google Scholar
• Fan C, Zhang H, Fu L, et al. Rett mutations attenuate phase separation of MeCP2. Cell Discov. 2020;6(1):38.
   PubMed Web of Science ®Google Scholar
• Casas-Delucchi CS, van Bemmel JG, Haase S, et al. Histone hypoacetylation is required to maintain late replication timing of constitutive heterochromatin. Nucleic Acids Res. 2012;40(1):159–169.
   PubMed Web of Science ®Google Scholar
• Chiang M, Brackley CA, Marenduzzo D, et al. Predicting genome organisation and function with mechanistic modelling. Trends Genet. 2022;38(4):364–378.
   PubMed Web of Science ®Google Scholar
• Schermelleh L, Haemmer A, Spada F, et al. Dynamics of Dnmt1 interaction with the replication machinery and its role in postreplicative maintenance of DNA methylation. Nucleic Acids Res. 2007;35(13):4301–4312.
   PubMed Web of Science ®Google Scholar
• Zhou FC, Resendiz M, C-L L, et al. Cell-Wide DNA de-methylation and re-methylation of purkinje neurons in the developing cerebellum. PLoS ONE. 2016;11(9):e0162063.
   PubMed Web of Science ®Google Scholar
• Piccolo FM, Liu Z, Dong P, et al. MeCP2 nuclear dynamics in live neurons results from low and high affinity chromatin interactions. eLife. 2019;8:e51449.
   PubMed Web of Science ®Google Scholar
• Agarwal N, Becker A, Jost KL, et al. MeCP2 Rett mutations affect large scale chromatin organization. Hum Mol Genet. 2011;20(21):4187–4195.
   PubMed Web of Science ®Google Scholar
• Casas-Delucchi CS, Becker A, Bolius JJ, et al. Targeted manipulation of heterochromatin rescues MeCP2 Rett mutants and re-establishes higher order chromatin organization. Nucleic Acids Res. 2012;40(22):e176.
   PubMed Web of Science ®Google Scholar
• Kernohan KD, Vernimmen D, Gloor GB, et al. Analysis of neonatal brain lacking ATRX or MeCP2 reveals changes in nucleosome density, CTCF binding and chromatin looping. Nucleic Acids Res. 2014;42(13):8356–8368.
   PubMed Web of Science ®Google Scholar
• Eissenberg JC, Elgin SC. The HP1 protein family: getting a grip on chromatin. Curr Opin Genet Dev. 2000;10(2):204–210.
   PubMed Web of Science ®Google Scholar
• Larson AG, Elnatan D, Keenen MM, et al. Liquid droplet formation by HP1α suggests a role for phase separation in heterochromatin. Nature. 2017;547(7662):236–240.
   PubMed Web of Science ®Google Scholar
• Keenen MM, Brown D, Brennan LD, et al. HP1 proteins compact DNA into mechanically and positionally stable phase separated domains. eLife. 2021;10:e64563.
   PubMed Web of Science ®Google Scholar
• Müller-Ott K, Erdel F, Matveeva A, et al. Specificity, propagation, and memory of pericentric heterochromatin. Mol Syst Biol. 2014;10(8):746.
   PubMed Web of Science ®Google Scholar
• Leicher R, Osunsade A, Chua GNL, et al. Single-stranded nucleic acid binding and coacervation by linker histone H1. Nat Struct Mol Biol. 2022;29:463–471.
   PubMed Web of Science ®Google Scholar
• Shakya A, Park S, Rana N, et al. Liquid-liquid phase separation of histone proteins in cells: role in chromatin organization. Biophys J. 2020;118(3):753–764.
   PubMed Web of Science ®Google Scholar
• Nielsen AL, Oulad-Abdelghani M, Ortiz JA, et al. Heterochromatin formation in mammalian cells: interaction between histones and HP1 proteins. Mol Cell. 2001;7(4):729–739.
   PubMed Web of Science ®Google Scholar
• Bannister AJ, Zegerman P, Partridge JF, et al. Selective recognition of methylated lysine 9 on histone H3 by the HP1 chromo domain. Nature. 2001;410(6824):120–124.
   PubMed Web of Science ®Google Scholar
• Jacobs SA, Khorasanizadeh S. Structure of HP1 chromodomain bound to a lysine 9-methylated histone H3 tail. Science. 2002;295(5562):2080–2083.
   PubMed Web of Science ®Google Scholar
• Nakayama J, Rice JC, Strahl BD, et al. Role of histone H3 lysine 9 methylation in epigenetic control of heterochromatin assembly. Science. 2001;292(5514):110–113.
   PubMed Web of Science ®Google Scholar
• Ainsztein AM, Kandels-Lewis SE, Mackay AM, et al. INCENP centromere and spindle targeting: identification of essential conserved motifs and involvement of heterochromatin protein HP1. J Cell Biol. 1998;143(7):1763–1774.
   PubMed Web of Science ®Google Scholar
• Ostapcuk V, Mohn F, Carl SH, et al. Activity-dependent neuroprotective protein recruits HP1 and CHD4 to control lineage-specifying genes. Nature. 2018;557(7707):739–743.
   PubMed Web of Science ®Google Scholar
• Quivy J-P, Gérard A, Cook AJL, et al. The HP1-p150/CAF-1 interaction is required for pericentric heterochromatin replication and S-phase progression in mouse cells. Nat Struct Mol Biol. 2008;15(9):972–979.
   PubMed Web of Science ®Google Scholar
• Ye Q, Worman HJ. Interaction between an integral protein of the nuclear envelope inner membrane and human chromodomain proteins homologous to Drosophila HP1. J Biol Chem. 1996;271(25):14653–14656.
   PubMed Web of Science ®Google Scholar
• Yamagishi Y, Sakuno T, Shimura M, et al. Heterochromatin links to centromeric protection by recruiting shugoshin. Nature. 2008;455(7210):251–255.
   PubMed Web of Science ®Google Scholar
• Markaki Y, Gan Chong J, Wang Y, et al. Xist nucleates local protein gradients to propagate silencing across the X chromosome. Cell. 2021;184(25):6174–6192.e32.
   PubMed Web of Science ®Google Scholar
• Conicella AE, Zerze GH, Mittal J, et al. ALS mutations disrupt phase separation mediated by α-helical structure in the TDP-43 low-complexity c-terminal domain. Structure. 2016;24(9):1537–1549.
   PubMed Web of Science ®Google Scholar
• McGurk L, Gomes E, Guo L, et al. Poly(ADP-Ribose) prevents pathological phase separation of TDP-43 by promoting liquid demixing and stress granule localization. Mol Cell. 2018;71(5):703–717.e9.
   PubMed Web of Science ®Google Scholar
• Muzzopappa F, Hertzog M, Erdel F. DNA length tunes the fluidity of DNA-based condensates. Biophys J. 2021;120(7):1288–1300.
   PubMed Web of Science ®Google Scholar
• Sanulli S, Trnka MJ, Dharmarajan V, et al. HP1 reshapes nucleosome core to promote phase separation of heterochromatin. Nature. 2019;575(7782):390–394.
   PubMed Web of Science ®Google Scholar