Phase separation and histone epigenetics in genome regulation
Source abstract
Abstract
Liquid-liquid phase separation is increasingly recognized as a phenomenon that affects cell behavior. For example, phase separation of transcription factors and coactivators has been shown to drive efficient transcription. For many years, phase separation of intracellular components has been observed; however, only recently have researchers been able to garner functional significance from such events. Inspired from recent literature that describes phase separation of chromatin in a histone-dependent manner, we review the role and effect of phase separation and histone epigenetics in regulating the genome and discuss how these phenomena can be leveraged to control cell behavior.
Source: europepmc · Quality: candidate unverified · Source record ↗
Research context
OpenAlex topics: Genomics and Chromatin Dynamics · RNA Research and Splicing · RNA Interference and Gene Delivery
SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.
References (93)
Show source-provided references
1. “Phase-separation in cytoplasm, due to macromolecular crowding, is the basis for microcompartmentation,” (in English)10.1016/0014-5793(95)00159-7 ↗
2. Structures and functions in the crowded nucleus: new biophysical insights10.3389/fphy.2014.00053 ↗
3. Atomic force microscopy for imaging human metaphase chromosomes10.1007/s10577-008-1241-7 ↗
4. The language of covalent histone modifications10.1038/47412 ↗
5. S. Palikyras, A. Papantonis, Modes of phase separation affecting chromatin regulation, Open Biol., vol. 9, no. 10, p. 190167, Oct 31 2019, 10.1098/rsob.190167.10.1098/rsob.190167 ↗
6. A.R. Strom, C.P. Brangwynne, The liquid nucleome - phase transitions in the nucleus at a glance, J. Cell. Sci., vol. 132, no. 22, Nov 21 2019, 10.1242/jcs.235093.10.1242/jcs.235093 ↗
7. Transcription factors and 3D genome conformation in cell-fate decisions10.1038/s41586-019-1182-7 ↗
8. Evaluating phase separation in live cells: diagnosis, caveats, and functional consequences10.1101/gad.331520.119 ↗
9. Y. Shin, C.P. Brangwynne, Liquid phase condensation in cell physiology and disease, Science, vol. 357, no. 6357, Sep 22 2017, 10.1126/science.aaf4382.10.1126/science.aaf4382 ↗
10. Regulation of ribosome biogenesis within the nucleolus10.1016/S0014-5793(01)03143-X ↗
11. RNA transcription modulates phase transition-driven nuclear body assembly10.1073/pnas.1509317112 ↗
12. Polymer physics of intracellular phase transitions10.1038/nphys3532 ↗
13. A phase separation model for transcriptional control10.1016/j.cell.2017.02.007 ↗
14. Transcription driven phase separation in chromatin brush10.1021/acs.langmuir.6b00442 ↗
15. A. Boija, et al., “Transcription Factors Activate Genes through the Phase-Separation Capacity of Their Activation Domains,” Cell, vol. 175, no. 7, pp. 1842-1855 e16, Dec 13 2018, 10.1016/j.cell.2018.10.042.10.1016/j.cell.2018.10.042 ↗
16. S. Chong, et al., Imaging dynamic and selective low-complexity domain interactions that control gene transcription, Science, vol. 361, no. 6400, Jul 27 2018, 10.1126/science.aar2555.10.1126/science.aar2555 ↗
17. Mediator and RNA polymerase II clusters associate in transcription-dependent condensates10.1126/science.aar4199 ↗
18. Phase separation of TAZ compartmentalizes the transcription machinery to promote gene expression10.1038/s41556-020-0485-0 ↗
19. B.R. Sabari, et al., Coactivator condensation at super-enhancers links phase separation and gene control, Science, vol. 361, no. 6400, Jul 27 2018, 10.1126/science.aar3958.
20. HP1 reshapes nucleosome core to promote phase separation of heterochromatin10.1038/s41586-019-1669-2 ↗
21. Evolving models of heterochromatin: from foci to liquid droplets10.1016/j.molcel.2017.08.022 ↗
22. B.A. Gibson, et al., Organization of chromatin by intrinsic and regulated phase separation, Cell, vol. 179, no. 2, pp. 470-484 e21, Oct 3 2019, 10.1016/j.cell.2019.08.037.10.1016/j.cell.2019.08.037 ↗
23. Phase separation of YAP reorganizes genome topology for long-term YAP target gene expression10.1038/s41556-019-0433-z ↗
24. Navigating the epigenetic landscape of pluripotent stem cells10.1038/nrm3393 ↗
25. Histone lysine methylation dynamics: establishment, regulation, and biological impact10.1016/j.molcel.2012.11.006 ↗
26. The power and the promise of DNA methylation markers10.1038/nrc1045 ↗
27. Translating the histone code10.1126/science.1063127 ↗
28. Genome-wide analysis of histone methylation reveals chromatin state-based regulation of gene transcription and function of memory CD8+ T cells10.1016/j.immuni.2009.05.006 ↗
29. Transcription regulation by histone methylation: interplay between different covalent modifications of the core histone tails10.1101/gad.927301 ↗
30. N.K. Yu, S.H. Baek, B.K. Kaang, DNA methylation-mediated control of learning and memory, Mol Brain, vol. 4, p. 5, Jan 19 2011, 10.1186/1756-6606-4-5.10.1186/1756-6606-4-5 ↗
31. H. Inaba, A. Tsukagoshi, S. Kida, PARP-1 activity is required for the reconsolidation and extinction of contextual fear memory, Mol Brain, vol. 8, no. 1, p. 63, Oct 15 2015, 10.1186/s13041-015-0153-7.10.1186/s13041-015-0153-7 ↗
32. Progress in epigenetic histone modification analysis by mass spectrometry for clinical investigations10.1586/14789450.2015.1084231 ↗
33. D. Han, et al., Lysine methylation of transcription factors in cancer, Cell Death Dis, vol. 10, no. 4, p. 290, Mar 29 2019, 10.1038/s41419-019-1524-2.10.1038/s41419-019-1524-2 ↗
34. Reversing histone methylation10.1038/nature04048 ↗
35. Regulation of chromatin by histone modifications10.1038/cr.2011.22 ↗
36. Protein arginine methylation in mammals: who, what, and why10.1016/j.molcel.2008.12.013 ↗
37. Dynamic protein methylation in chromatin biology10.1007/s00018-008-8303-z ↗
38. The SET-domain protein superfamily: protein lysine methyltransferases10.1186/gb-2005-6-8-227 ↗
39. Subunit composition and substrate specificity of a MOF-containing histone acetyltransferase distinct from the male-specific lethal (MSL) complex10.1074/jbc.C109.087981 ↗
40. Erasing the methyl mark: histone demethylases at the center of cellular differentiation and disease10.1101/gad.1652908 ↗
41. Acetylation and methylation of histones and their possible role in the regulation of Rna synthesis10.1073/pnas.51.5.786 ↗
42. Roles of histone acetyltransferases and deacetylases in gene regulation10.1002/(SICI)1521-1878(199808)20:8<615::AID-BIES4>3.0.CO;2-H ↗
43. M. Oki, H. Aihara, T. Ito, Role of histone phosphorylation in chromatin dynamics and its implications in diseases, Subcell Biochem, vol. 41, pp. 319-36, 2007. [Online]. Available: https://www.ncbi.nlm.nih.gov/pubmed/17484134.
44. Chromatin-associated protein phosphatase 1 regulates aurora-B and histone H3 phosphorylation10.1074/jbc.M102288200 ↗
45. Chromatin modifications and their function10.1016/j.cell.2007.02.005 ↗
46. Histone acetylation: a switch between repressive and permissive chromatin. Second in review series on chromatin dynamics10.1093/embo-reports/kvf053 ↗
47. Role of histone acetylation in the control of gene expression10.1139/o05-041 ↗
48. Histone H4–K16 acetylation controls chromatin structure and protein interactions10.1126/science.1124000 ↗
49. Switching on chromatin: mechanistic role of histone H4–K16 acetylation10.4161/cc.5.13.2891 ↗
50. Histone phosphorylation: a chromatin modification involved in diverse nuclear events10.4161/epi.21975 ↗
51. Ezh1 and Ezh2 maintain repressive chromatin through different mechanisms10.1016/j.molcel.2008.11.004 ↗
52. Multivalent engagement of chromatin modifications by linked binding modules10.1038/nrm2298 ↗
53. Y. Wu, et al., miR-29a contributes to breast cancer cells epithelial-mesenchymal transition, migration, and invasion via down-regulating histone H4K20 trimethylation through directly targeting SUV420H2, Cell Death Dis, vol. 10, no. 3, p. 176, Feb 21 2019, 10.1038/s41419-019-1437-0.10.1038/s41419-019-1437-0 ↗
54. Heterochromatin protein 1 is recruited to various types of DNA damage10.1083/jcb.200810035 ↗
55. Chromatin unfolding by epigenetic modifications explained by dramatic impairment of internucleosome interactions: a multiscale computational study10.1021/jacs.5b04086 ↗
56. Super-resolution microscopy reveals how histone tail acetylation affects DNA compaction within nucleosomes in vivo10.1093/nar/gkz593 ↗
57. H. Zhu, T. Wei, Y. Cai, J. Jin, Small molecules targeting the specific domains of histone-mark readers in cancer therapy, Molecules, vol. 25, no. 3, Jan 29 2020, 10.3390/molecules25030578.10.3390/molecules25030578 ↗
58. Readers of histone modifications10.1038/cr.2011.42 ↗
59. Keeping it in the family: diverse histone recognition by conserved structural folds10.3109/10409238.2010.512001 ↗
60. Structure of H3K36-methylated nucleosome-PWWP complex reveals multivalent cross-gyre binding10.1038/s41594-019-0345-4 ↗
61. ING2 PHD domain links histone H3 lysine 4 methylation to active gene repression10.1038/nature04835 ↗
62. K. Miura, N. Renhu, T. Suzaki, The PHD finger of Arabidopsis SIZ1 recognizes trimethylated histone H3K4 mediating SIZ1 function and abiotic stress response, Commun. Biol., vol. 3, no. 1, p. 23, Jan 10 2020, 10.1038/s42003-019-0746-2.10.1038/s42003-019-0746-2 ↗
63. WD40 repeat domain proteins: a novel target class?10.1038/nrd.2017.179 ↗
64. Bromodomain biology and drug discovery10.1038/s41594-019-0309-8 ↗
65. Structure and ligand of a histone acetyltransferase bromodomain10.1038/20974 ↗
66. Epigenetic tools (The Writers, The Readers and The Erasers) and their implications in cancer therapy10.1016/j.ejphar.2018.08.021 ↗
67. Distinct and predictive chromatin signatures of transcriptional promoters and enhancers in the human genome10.1038/ng1966 ↗
68. E.P. Consortium, et al., Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project, Nature, vol. 447, no. 7146, pp. 799-816, Jun 14 2007, 10.1038/nature05874.10.1038/nature05874 ↗
69. Methylation of lysine 4 on histone H3: intricacy of writing and reading a single epigenetic mark10.1016/j.molcel.2006.12.014 ↗
70. Is H3K4me3 instructive for transcription activation?10.1002/bies.201600095 ↗
71. Acetylation on histone H3 lysine 9 mediates a switch from transcription initiation to elongation10.1074/jbc.M117.802074 ↗
72. Selective anchoring of TFIID to nucleosomes by trimethylation of histone H3 lysine 410.1016/j.cell.2007.08.016 ↗
73. Perceiving the epigenetic landscape through histone readers10.1038/nsmb.2436 ↗
74. H3K36 methylation antagonizes PRC2-mediated H3K27 methylation10.1074/jbc.M110.194027 ↗
75. Histone methylation by PRC2 is inhibited by active chromatin marks10.1016/j.molcel.2011.03.025 ↗
76. Liquid-liquid phase separation is an intrinsic physicochemical property of chromatin10.1038/s41594-019-0333-8 ↗
77. Liquid droplet formation by HP1alpha suggests a role for phase separation in heterochromatin10.1038/nature22822 ↗
78. Phase separation drives heterochromatin domain formation10.1038/nature22989 ↗
79. Nuclear condensates of the Polycomb protein chromobox 2 (CBX2) assemble through phase separation10.1074/jbc.RA118.006620 ↗
80. Plant HP1 protein ADCP1 links multivalent H3K9 methylation readout to heterochromatin formation10.1038/s41422-018-0104-9 ↗
81. Phase separation of Polycomb-repressive complex 1 is governed by a charged disordered region of CBX210.1101/gad.326488.119 ↗
82. Highly disordered histone H1-DNA model complexes and their condensates10.1073/pnas.1805943115 ↗
83. Phase separation directs ubiquitination of gene-body nucleosomes10.1038/s41586-020-2097-z ↗
84. Roles of the BRD4 short isoform in phase separation and active gene transcription10.1038/s41594-020-0394-8 ↗
85. L. Wang, et al., Histone modifications regulate chromatin compartmentalization by contributing to a phase separation mechanism, Mol Cell, vol. 76, no. 4, pp. 646-659 e6, Nov 21 2019, 10.1016/j.molcel.2019.08.019.10.1016/j.molcel.2019.08.019 ↗
86. HP1 binds specifically to Lys26-methylated histone H1.4, whereas simultaneous Ser27 phosphorylation blocks HP1 binding10.1074/jbc.C500229200 ↗
87. Piwi modulates chromatin accessibility by regulating multiple factors including histone H1 to repress transposons10.1016/j.molcel.2016.06.008 ↗
88. Heterochromatin formation in mammalian cells: interaction between histones and HP1 proteins10.1016/S1097-2765(01)00218-0 ↗
89. Improvements to the APBS biomolecular solvation software suite10.1002/pro.3280 ↗
90. Acetylation of intrinsically disordered regions regulates phase separation10.1038/s41589-018-0180-7 ↗
91. Phosphorylation of the linker histone H1 by CDK regulates its binding to HP1alpha10.1016/j.molcel.2006.04.016 ↗
92. Liquid-liquid phase separation of histone proteins in cells: role in chromatin organization10.1016/j.bpj.2019.12.022 ↗
93. Genome regulation by polycomb and trithorax: 70 years and counting10.1016/j.cell.2017.08.002 ↗