PML is Recruited to Heterochromatin During S Phase and Represses DAXX-mediated Histone H3.3 Chromatin Assembly

Overview

Journal J Cell Sci

Specialty Cell Biology

Date 2019 Feb 24

PMID 30796101

Citations 16

Authors

Prashanth Krishna Shastrula

Isabel Sierra

Zhong Deng

Frederick Keeney

James E Hayden

Paul M Lieberman

Susan M Janicki

Affiliations

Soon will be listed here.

Abstract

The incorporation of the histone H3 variant, H3.3, into chromatin by the H3.3-specific chaperone DAXX and the ATP-dependent chromatin remodeling factor ATRX is a critical mechanism for silencing repetitive DNA. DAXX and ATRX are also components of promyelocytic nuclear bodies (PML-NBs), which have been identified as sites of H3.3 chromatin assembly. Here, we use a transgene array that can be visualized in single living cells to investigate the mechanisms that recruit PML-NB proteins (i.e. PML, DAXX, ATRX, and SUMO-1, SUMO-2 and SUMO-3) to heterochromatin and their functions in H3.3 chromatin assembly. We show that DAXX and PML are recruited to the array through distinct SUMOylation-dependent mechanisms. Additionally, PML is recruited during S phase and its depletion increases H3.3 deposition. Since this effect is abrogated when PML and DAXX are co-depleted, it is likely that PML represses DAXX-mediated H3.3 chromatin assembly. Taken together, these results suggest that, at heterochromatin, PML-NBs coordinate H3.3 chromatin assembly with DNA replication, which has important implications for understanding how transcriptional silencing is established and maintained.

Citing Articles

Mutant ATRX: pathogenesis of ATRX syndrome and cancer.

Yuan K, Tang Y, Ding Z, Peng L, Zeng J, Wu H Front Mol Biosci. 2024; 11:1434398.

PMID: 39479502 PMC: 11521912. DOI: 10.3389/fmolb.2024.1434398.

On the Prevalence and Roles of Proteins Undergoing Liquid-Liquid Phase Separation in the Biogenesis of PML-Bodies.

Silonov S, Mokin Y, Nedelyaev E, Smirnov E, Kuznetsova I, Turoverov K Biomolecules. 2023; 13(12).

PMID: 38136675 PMC: 10741438. DOI: 10.3390/biom13121805.

PML-mediated nuclear loosening permits immunomodulation of mesenchymal stem/stromal cells under inflammatory conditions.

Chu Y, Jiang Z, Gong Z, Ji X, Zhu M, Shang Q Cell Prolif. 2023; 57(4):e13566.

PMID: 37864298 PMC: 10984101. DOI: 10.1111/cpr.13566.

PML modulates epigenetic composition of chromatin to regulate expression of pro-metastatic genes in triple-negative breast cancer.

Fracassi C, Ugge M, Abdelhalim M, Zapparoli E, Simoni M, Magliulo D Nucleic Acids Res. 2023; 51(20):11024-11039.

PMID: 37823593 PMC: 10639071. DOI: 10.1093/nar/gkad819.

Chromatin control of human cytomegalovirus infection.

Matthews S, Groves I, OConnor C mBio. 2023; 14(4):e0032623.

PMID: 37439556 PMC: 10470543. DOI: 10.1128/mbio.00326-23.

References

Johnson E . Protein modification by SUMO. Annu Rev Biochem. 2004; 73:355-82. DOI: 10.1146/annurev.biochem.73.011303.074118. View

He Q, Kim H, Huang R, Lu W, Tang M, Shi F . The Daxx/Atrx Complex Protects Tandem Repetitive Elements during DNA Hypomethylation by Promoting H3K9 Trimethylation. Cell Stem Cell. 2015; 17(3):273-86. PMC: 4571182. DOI: 10.1016/j.stem.2015.07.022. View

Cohen C, Corpet A, Roubille S, Maroui M, Poccardi N, Rousseau A . Promyelocytic leukemia (PML) nuclear bodies (NBs) induce latent/quiescent HSV-1 genomes chromatinization through a PML NB/Histone H3.3/H3.3 Chaperone Axis. PLoS Pathog. 2018; 14(9):e1007313. PMC: 6168178. DOI: 10.1371/journal.ppat.1007313. View

Boutell C, Orr A, Everett R . PML residue lysine 160 is required for the degradation of PML induced by herpes simplex virus type 1 regulatory protein ICP0. J Virol. 2003; 77(16):8686-94. PMC: 167235. DOI: 10.1128/jvi.77.16.8686-8694.2003. View

Shastrula P, Lund P, Garcia B, Janicki S . Rpp29 regulates histone H3.3 chromatin assembly through transcriptional mechanisms. J Biol Chem. 2018; 293(32):12360-12377. PMC: 6093239. DOI: 10.1074/jbc.RA118.001845. View

Lin D, Tatham M, Yu B, Kim S, Hay R, Chen Y . Identification of a substrate recognition site on Ubc9. J Biol Chem. 2002; 277(24):21740-8. DOI: 10.1074/jbc.M108418200. View

Lukashchuk V, McFarlane S, Everett R, Preston C . Human cytomegalovirus protein pp71 displaces the chromatin-associated factor ATRX from nuclear domain 10 at early stages of infection. J Virol. 2008; 82(24):12543-54. PMC: 2593304. DOI: 10.1128/JVI.01215-08. View

Rafalska-Metcalf I, Janicki S . Preparation of cell lines for single-cell analysis of transcriptional activation dynamics. Methods Mol Biol. 2013; 977:249-58. DOI: 10.1007/978-1-62703-284-1_20. View

Tagami H, Ray-Gallet D, Almouzni G, Nakatani Y . Histone H3.1 and H3.3 complexes mediate nucleosome assembly pathways dependent or independent of DNA synthesis. Cell. 2004; 116(1):51-61. DOI: 10.1016/s0092-8674(03)01064-x. View

10.

Voon H, Hughes J, Rode C, de la Rosa-Velazquez I, Jenuwein T, Feil R . ATRX Plays a Key Role in Maintaining Silencing at Interstitial Heterochromatic Loci and Imprinted Genes. Cell Rep. 2015; 11(3):405-18. PMC: 4410944. DOI: 10.1016/j.celrep.2015.03.036. View

11.

Huether R, Dong L, Chen X, Wu G, Parker M, Wei L . The landscape of somatic mutations in epigenetic regulators across 1,000 paediatric cancer genomes. Nat Commun. 2014; 5:3630. PMC: 4119022. DOI: 10.1038/ncomms4630. View

12.

Drane P, Ouararhni K, Depaux A, Shuaib M, Hamiche A . The death-associated protein DAXX is a novel histone chaperone involved in the replication-independent deposition of H3.3. Genes Dev. 2010; 24(12):1253-65. PMC: 2885661. DOI: 10.1101/gad.566910. View

13.

Fulka H, Langerova A . The maternal nucleolus plays a key role in centromere satellite maintenance during the oocyte to embryo transition. Development. 2014; 141(8):1694-704. DOI: 10.1242/dev.105940. View

14.

Voon H, Wong L . New players in heterochromatin silencing: histone variant H3.3 and the ATRX/DAXX chaperone. Nucleic Acids Res. 2016; 44(4):1496-501. PMC: 4770241. DOI: 10.1093/nar/gkw012. View

15.

Lallemand-Breitenbach V, de The H . PML nuclear bodies. Cold Spring Harb Perspect Biol. 2010; 2(5):a000661. PMC: 2857171. DOI: 10.1101/cshperspect.a000661. View

16.

Everett R, Lomonte P, Sternsdorf T, VAN Driel R, Orr A . Cell cycle regulation of PML modification and ND10 composition. J Cell Sci. 1999; 112 ( Pt 24):4581-8. DOI: 10.1242/jcs.112.24.4581. View

17.

Lang M, Jegou T, Chung I, Richter K, Munch S, Udvarhelyi A . Three-dimensional organization of promyelocytic leukemia nuclear bodies. J Cell Sci. 2010; 123(Pt 3):392-400. DOI: 10.1242/jcs.053496. View

18.

Gibbons R, Picketts D, Villard L, Higgs D . Mutations in a putative global transcriptional regulator cause X-linked mental retardation with alpha-thalassemia (ATR-X syndrome). Cell. 1995; 80(6):837-45. DOI: 10.1016/0092-8674(95)90287-2. View

19.

Shiels C, Islam S, Vatcheva R, Sasieni P, STERNBERG M, Freemont P . PML bodies associate specifically with the MHC gene cluster in interphase nuclei. J Cell Sci. 2001; 114(Pt 20):3705-16. DOI: 10.1242/jcs.114.20.3705. View

20.

Luciani J, Depetris D, Usson Y, Metzler-Guillemain C, Mignon-Ravix C, Mitchell M . PML nuclear bodies are highly organised DNA-protein structures with a function in heterochromatin remodelling at the G2 phase. J Cell Sci. 2006; 119(Pt 12):2518-31. DOI: 10.1242/jcs.02965. View