Silencing Markers Are Retained on Pericentric Heterochromatin During Murine Primordial Germ Cell Development

Overview

Journal Epigenetics Chromatin

Publisher Biomed Central

Specialties Biochemistry
Genetics

Date 2017 Mar 16

PMID 28293300

Citations 16

Authors

Aristea Magaraki

Godfried van der Heijden

Esther Sleddens-Linkels

Leonidas Magarakis

Wiggert A van Cappellen

Antoine H F M Peters

Joost Gribnau

Willy M Baarends

Maureen Eijpe

Affiliations

Soon will be listed here.

Abstract

Background: In the nuclei of most mammalian cells, pericentric heterochromatin is characterized by DNA methylation, histone modifications such as H3K9me3 and H4K20me3, and specific binding proteins like heterochromatin-binding protein 1 isoforms (HP1 isoforms). Maintenance of this specialized chromatin structure is of great importance for genome integrity and for the controlled repression of the repetitive elements within the pericentric DNA sequence. Here we have studied histone modifications at pericentric heterochromatin during primordial germ cell (PGC) development using different fixation conditions and fluorescent immunohistochemical and immunocytochemical protocols.

Results: We observed that pericentric heterochromatin marks, such as H3K9me3, H4K20me3, and HP1 isoforms, were retained on pericentric heterochromatin throughout PGC development. However, the observed immunostaining patterns varied, depending on the fixation method, explaining previous findings of a general loss of pericentric heterochromatic features in PGCs. Also, in contrast to the general clustering of multiple pericentric regions and associated centromeres in DAPI-dense regions in somatic cells, the pericentric regions of PGCs were more frequently organized as individual entities. We also observed a transient enrichment of the chromatin remodeler ATRX in pericentric regions in embryonic day 11.5 (E11.5) PGCs. At this stage, a similar and low level of major satellite repeat RNA transcription was detected in both PGCs and somatic cells.

Conclusions: These results indicate that in pericentric heterochromatin of mouse PGCs, only minor reductions in levels of some chromatin-associated proteins occur, in association with a transient increase in ATRX, between E11.5 and E13.5. These pericentric heterochromatin regions more frequently contain only a single centromere in PGCs compared to the surrounding soma, indicating a difference in overall organization, but there is no de-repression of major satellite transcription.

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References

Takada Y, Naruse C, Costa Y, Shirakawa T, Tachibana M, Sharif J . HP1γ links histone methylation marks to meiotic synapsis in mice. Development. 2011; 138(19):4207-17. DOI: 10.1242/dev.064444. View

Peters A, Kubicek S, Mechtler K, OSullivan R, Derijck A, Perez-Burgos L . Partitioning and plasticity of repressive histone methylation states in mammalian chromatin. Mol Cell. 2003; 12(6):1577-89. DOI: 10.1016/s1097-2765(03)00477-5. View

Lehnertz B, Ueda Y, Derijck A, Braunschweig U, Perez-Burgos L, Kubicek S . Suv39h-mediated histone H3 lysine 9 methylation directs DNA methylation to major satellite repeats at pericentric heterochromatin. Curr Biol. 2003; 13(14):1192-200. DOI: 10.1016/s0960-9822(03)00432-9. View

De La Fuente R, Baumann C, Viveiros M . ATRX contributes to epigenetic asymmetry and silencing of major satellite transcripts in the maternal genome of the mouse embryo. Development. 2015; 142(10):1806-17. PMC: 4440925. DOI: 10.1242/dev.118927. View

McDowell T, Gibbons R, Sutherland H, ORourke D, Bickmore W, Pombo A . Localization of a putative transcriptional regulator (ATRX) at pericentromeric heterochromatin and the short arms of acrocentric chromosomes. Proc Natl Acad Sci U S A. 1999; 96(24):13983-8. PMC: 24177. DOI: 10.1073/pnas.96.24.13983. View

Sadic D, Schmidt K, Groh S, Kondofersky I, Ellwart J, Fuchs C . Atrx promotes heterochromatin formation at retrotransposons. EMBO Rep. 2015; 16(7):836-50. PMC: 4515123. DOI: 10.15252/embr.201439937. View

Hajkova P, Erhardt S, Lane N, Haaf T, El-Maarri O, Reik W . Epigenetic reprogramming in mouse primordial germ cells. Mech Dev. 2002; 117(1-2):15-23. DOI: 10.1016/s0925-4773(02)00181-8. View

Baumann C, Schmidtmann A, Muegge K, De La Fuente R . Association of ATRX with pericentric heterochromatin and the Y chromosome of neonatal mouse spermatogonia. BMC Mol Biol. 2008; 9:29. PMC: 2275742. DOI: 10.1186/1471-2199-9-29. View

Lu J, Gilbert D . Proliferation-dependent and cell cycle regulated transcription of mouse pericentric heterochromatin. J Cell Biol. 2007; 179(3):411-21. PMC: 2064789. DOI: 10.1083/jcb.200706176. View

10.

Maze I, Feng J, Wilkinson M, Sun H, Shen L, Nestler E . Cocaine dynamically regulates heterochromatin and repetitive element unsilencing in nucleus accumbens. Proc Natl Acad Sci U S A. 2011; 108(7):3035-40. PMC: 3041122. DOI: 10.1073/pnas.1015483108. View

11.

Guenatri M, Bailly D, Maison C, Almouzni G . Mouse centric and pericentric satellite repeats form distinct functional heterochromatin. J Cell Biol. 2004; 166(4):493-505. PMC: 2172221. DOI: 10.1083/jcb.200403109. View

12.

Kagiwada S, Kurimoto K, Hirota T, Yamaji M, Saitou M . Replication-coupled passive DNA demethylation for the erasure of genome imprints in mice. EMBO J. 2012; 32(3):340-53. PMC: 3567490. DOI: 10.1038/emboj.2012.331. View

13.

Yoshimizu T, Sugiyama N, De Felice M, Yeom Y, Ohbo K, Masuko K . Germline-specific expression of the Oct-4/green fluorescent protein (GFP) transgene in mice. Dev Growth Differ. 2000; 41(6):675-84. DOI: 10.1046/j.1440-169x.1999.00474.x. View

14.

Fussner E, Djuric U, Strauss M, Hotta A, Perez-Iratxeta C, Lanner F . Constitutive heterochromatin reorganization during somatic cell reprogramming. EMBO J. 2011; 30(9):1778-89. PMC: 3102001. DOI: 10.1038/emboj.2011.96. View

15.

Ohinata Y, Ohta H, Shigeta M, Yamanaka K, Wakayama T, Saitou M . A signaling principle for the specification of the germ cell lineage in mice. Cell. 2009; 137(3):571-84. DOI: 10.1016/j.cell.2009.03.014. View

16.

Santos F, Hendrich B, Reik W, Dean W . Dynamic reprogramming of DNA methylation in the early mouse embryo. Dev Biol. 2002; 241(1):172-82. DOI: 10.1006/dbio.2001.0501. View

17.

Rea S, Eisenhaber F, OCarroll D, Strahl B, Sun Z, Schmid M . Regulation of chromatin structure by site-specific histone H3 methyltransferases. Nature. 2000; 406(6796):593-9. DOI: 10.1038/35020506. View

18.

van der Heijden G, Dieker J, Derijck A, Muller S, Berden J, Braat D . Asymmetry in histone H3 variants and lysine methylation between paternal and maternal chromatin of the early mouse zygote. Mech Dev. 2005; 122(9):1008-22. DOI: 10.1016/j.mod.2005.04.009. View

19.

Hill P, Amouroux R, Hajkova P . DNA demethylation, Tet proteins and 5-hydroxymethylcytosine in epigenetic reprogramming: an emerging complex story. Genomics. 2014; 104(5):324-33. DOI: 10.1016/j.ygeno.2014.08.012. View

20.

Ishov A, Vladimirova O, Maul G . Heterochromatin and ND10 are cell-cycle regulated and phosphorylation-dependent alternate nuclear sites of the transcription repressor Daxx and SWI/SNF protein ATRX. J Cell Sci. 2004; 117(Pt 17):3807-20. DOI: 10.1242/jcs.01230. View