Grewal, S. I. S. The molecular basis of heterochromatin assembly and epigenetic inheritance. Mol. Cell 83, 1767–1785 (2023).
Padeken, J., Methot, S. P. & Gasser, S. M. Establishment of H3K9-methylated heterochromatin and its functions in tissue differentiation and maintenance. Nat. Rev. Mol. Cell Biol. 23, 623–640 (2022).
Allshire, R. C. & Madhani, H. D. Ten principles of heterochromatin formation and function. Nat. Rev. Mol. Cell Biol. 19, 229–244 (2018).
Ghosh, R. P. & Meyer, B. J. Spatial organization of chromatin: emergence of chromatin structure during development. Annu. Rev. Cell Dev. Biol. 37, 199–232 (2021).
Saksouk, N., Simboeck, E. & Dejardin, J. Constitutive heterochromatin formation and transcription in mammals. Epigenet. Chromatin 8, 3 (2015).
Janssen, A., Colmenares, S. U. & Karpen, G. H. Heterochromatin: guardian of the genome. Annu. Rev. Cell Dev. Biol. 34, 265–288 (2018).
Penagos-Puig, A. & Furlan-Magaril, M. Heterochromatin as an important driver of genome organization. Front. Cell Dev. Biol. 8, 579137 (2020).
Chen, P., Li, W. & Li, G. Structures and functions of chromatin fibers. Annu. Rev. Biophys. 50, 95–116 (2021).
Ma, R. et al. Targeting pericentric non-consecutive motifs for heterochromatin initiation. Nature 631, 678–685 (2024).
Yu, R., Wang, X. & Moazed, D. Epigenetic inheritance mediated by coupling of RNAi and histone H3K9 methylation. Nature 558, 615–619 (2018).
Montavon, T. et al. Complete loss of H3K9 methylation dissolves mouse heterochromatin organization. Nat. Commun. 12, 4359 (2021).
Nakayama, J., Rice, J. C., Strahl, B. D., Allis, C. D. & Grewal, S. I. Role of histone H3 lysine 9 methylation in epigenetic control of heterochromatin assembly. Science 292, 110–113 (2001).
Peters, A. H. et al. Loss of the Suv39h histone methyltransferases impairs mammalian heterochromatin and genome stability. Cell 107, 323–337 (2001).
Bannister, A. J. et al. Selective recognition of methylated lysine 9 on histone H3 by the HP1 chromo domain. Nature 410, 120–124 (2001).
Lachner, M., O’Carroll, D., Rea, S., Mechtler, K. & Jenuwein, T. Methylation of histone H3 lysine 9 creates a binding site for HP1 proteins. Nature 410, 116–120 (2001).
Lomberk, G., Wallrath, L. & Urrutia, R. The heterochromatin protein 1 family. Genome Biol. 7, 228 (2006).
Zenk, F. et al. HP1 drives de novo 3D genome reorganization in early Drosophila embryos. Nature 593, 289–293 (2021).
Hong, E. J., Villen, J., Gerace, E. L., Gygi, S. P. & Moazed, D. A cullin E3 ubiquitin ligase complex associates with Rik1 and the Clr4 histone H3-K9 methyltransferase and is required for RNAi-mediated heterochromatin formation. RNA Biol. 2, 106–111 (2005).
Horn, P. J., Bastie, J. N. & Peterson, C. L. A Rik1-associated, cullin-dependent E3 ubiquitin ligase is essential for heterochromatin formation. Genes Dev. 19, 1705–1714 (2005).
Jia, S., Kobayashi, R. & Grewal, S. I. Ubiquitin ligase component Cul4 associates with Clr4 histone methyltransferase to assemble heterochromatin. Nat. Cell Biol. 7, 1007–1013 (2005).
Oya, E. et al. H3K14 ubiquitylation promotes H3K9 methylation for heterochromatin assembly. EMBO Rep. 20, e48111 (2019).
Stirpe, A. et al. SUV39 SET domains mediate crosstalk of heterochromatic histone marks. eLife 10, e62682 (2021).
Cao, X. et al. Histone H4K20 demethylation by two hHR23 proteins. Cell Rep. 30, 4152–4164 (2020).
Yang, S. Y., Baxter, E. M. & Van Doren, M. Phf7 controls male sex determination in the Drosophila germline. Dev. Cell 22, 1041–1051 (2012).
Kim, C. R. et al. PHF7 modulates BRDT stability and histone-to-protamine exchange during spermiogenesis. Cell Rep. 32, 107950 (2020).
Brooks, W. S. et al. G2E3 is a dual function ubiquitin ligase required for early embryonic development. J. Biol. Chem. 283, 22304–22315 (2008).
Brooks, W. S., Banerjee, S. & Crawford, D. F. G2E3 is a nucleo-cytoplasmic shuttling protein with DNA damage responsive localization. Exp. Cell. Res. 313, 665–676 (2007).
Crawford, D. F. & Piwnica-Worms, H. The G2 DNA damage checkpoint delays expression of genes encoding mitotic regulators. J. Biol. Chem. 276, 37166–37177 (2001).
Fischle, W. et al. Regulation of HP1-chromatin binding by histone H3 methylation and phosphorylation. Nature 438, 1116–1122 (2005).
Hirota, T., Lipp, J. J., Toh, B. H. & Peters, J. M. Histone H3 serine 10 phosphorylation by Aurora B causes HP1 dissociation from heterochromatin. Nature 438, 1176–1180 (2005).
Aagaard, L., Schmid, M., Warburton, P. & Jenuwein, T. Mitotic phosphorylation of SUV39H1, a novel component of active centromeres, coincides with transient accumulation at mammalian centromeres. J. Cell Sci. 113, 817–829 (2000).
Li, X. & Fu, X. D. Chromatin-associated RNAs as facilitators of functional genomic interactions. Nat. Rev. Genet. 20, 503–519 (2019).
Martienssen, R. & Moazed, D. RNAi and heterochromatin assembly. Cold Spring Harbor Perspect. Biol. 7, a019323 (2015).
Motamedi, M. R. et al. Two RNAi complexes, RITS and RDRC, physically interact and localize to noncoding centromeric RNAs. Cell 119, 789–802 (2004).
Buhler, M., Verdel, A. & Moazed, D. Tethering RITS to a nascent transcript initiates RNAi- and heterochromatin-dependent gene silencing. Cell 125, 873–886 (2006).
Maison, C. et al. Higher-order structure in pericentric heterochromatin involves a distinct pattern of histone modification and an RNA component. Nat. Genet. 30, 329–334 (2002).
Johnson, W. L. et al. RNA-dependent stabilization of SUV39H1 at constitutive heterochromatin. eLife 6, e25299 (2017).
Velazquez Camacho, O. et al. Major satellite repeat RNA stabilize heterochromatin retention of Suv39h enzymes by RNA-nucleosome association and RNA:DNA hybrid formation. eLife 6, e25293 (2017).
Shirai, A. et al. Impact of nucleic acid and methylated H3K9 binding activities of Suv39h1 on its heterochromatin assembly. eLife 6, e25317 (2017).
Al-Sady, B., Madhani, H. D. & Narlikar, G. J. Division of labor between the chromodomains of HP1 and Suv39 methylase enables coordination of heterochromatin spread. Mol. Cell 51, 80–91 (2013).
Zhang, K., Mosch, K., Fischle, W. & Grewal, S. I. Roles of the Clr4 methyltransferase complex in nucleation, spreading and maintenance of heterochromatin. Nat. Struct. Mol. Biol. 15, 381–388 (2008).
Horita, D. A., Ivanova, A. V., Altieri, A. S., Klar, A. J. S. & Byrd, R. A. Solution structure, domain features, and structural implications of mutants of the chromo domain from the fission yeast histone methyltransferase Clr4. J. Mol. Biol. 307, 861–870 (2001).
Jacobs, S. A. & Khorasanizadeh, S. Structure of HP1 chromodomain bound to a lysine 9-methylated histone H3 tail. Science 295, 2080–2083 (2002).
Nielsen, P. R. et al. Structure of the HP1 chromodomain bound to histone H3 methylated at lysine 9. Nature 416, 103–107 (2002).
Wang, T. et al. Crystal structure of the human SUV39H1 chromodomain and its recognition of histone H3K9me2/3. PLoS ONE 7, e52977 (2012).
Rowe, H. M. et al. KAP1 controls endogenous retroviruses in embryonic stem cells. Nature 463, 237–240 (2010).
Xu, W. et al. METTL3 regulates heterochromatin in mouse embryonic stem cells. Nature 591, 317–321 (2021).
Hall, I. M. et al. Establishment and maintenance of a heterochromatin domain. Science 297, 2232–2237 (2002).
Volpe, T. A. et al. Regulation of heterochromatic silencing and histone H3 lysine-9 methylation by RNAi. Science 297, 1833–1837 (2002).
Khanduja, J. S. et al. RNA quality control factors nucleate Clr4/SUV39H and trigger constitutive heterochromatin assembly. Cell 187, 3262–3283 (2024).
Ran, F. A. et al. Genome engineering using the CRISPR-Cas9 system. Nat. Protoc. 8, 2281–2308 (2013).
Liu, C., Zhao, J. & Li, G. Preparation and characterization of chromatin templates for histone methylation assays. Methods Mol. Biol. 2529, 91–107 (2022).
Li, J. et al. USP7 negatively controls global DNA methylation by attenuating ubiquitinated histone-dependent DNMT1 recruitment. Cell Discov. 6, 58 (2020).
Jumper, J. et al. Highly accurate protein structure prediction with AlphaFold. Nature 596, 583–589 (2021).
Kozakov, D. et al. The ClusPro web server for protein–protein docking. Nat. Protoc. 12, 255–278 (2017).
Abad, P. C. et al. NuMA influences higher order chromatin organization in human mammary epithelium. Mol. Biol. Cell 18, 348–361 (2007).
Langmead, B. & Salzberg, S. L. Fast gapped-read alignment with Bowtie 2. Nat. Methods 9, 357–U354 (2012).
Zhang, Y. et al. Model-based analysis of ChIP-Seq (MACS). Genome Biol. 9, R137 (2008).
Ramirez, F. et al. deepTools2: a next generation web server for deep-sequencing data analysis. Nucleic Acids Res. 44, W160–W165 (2016).
Heinz, S. et al. Simple combinations of lineage-determining transcription factors prime cis-regulatory elements required for macrophage and B cell identities. Mol. Cell 38, 576–589 (2010).
Dobin, A. et al. STAR: ultrafast universal RNA-seq aligner. Bioinformatics 29, 15–21 (2013).
Liao, Y., Smyth, G. K. & Shi, W. featureCounts: an efficient general purpose program for assigning sequence reads to genomic features. Bioinformatics 30, 923–930 (2014).
Xie, M. C. et al. DNA hypomethylation within specific transposable element families associates with tissue-specific enhancer landscape. Nat. Genet. 45, 836–841 (2013).
