Expression of SNURF-SNRPN Upstream Transcripts and Epigenetic Regulatory Genes During Human Spermatogenesis

Overview

Journal Eur J Hum Genet

Specialty Genetics

Date 2009 May 28

PMID 19471314

Citations 16

Authors

Michaela Wawrzik

Andrej-Nikolai Spiess

Ralf Herrmann

Karin Buiting

Bernhard Horsthemke

Affiliations

Soon will be listed here.

Abstract

The imprinted domain in human 15q11-q13 is controlled by a bipartite imprinting centre (IC), which overlaps the 5' part of the paternally expressed SNURF-SNRPN gene. We have recently described two novel genes upstream of SNURF-SNRPN (PWRN1 and PWRN2), which are biallelically expressed in the testis. We have now found that PWRN1 represents an alternative 5' part of SNURF-SNRPN, and that its expression in the brain is imprinted. To determine when the locus is activated during spermatogenesis and which factors are involved in this process, we have mined gene-expression data of testicular biopsies from men with different types of spermatogenic failure. Whereas PWRN1-SNURF-SNRPN and PWRN2 are expressed in post-meiotic germ cells only, a hitherto undetected SNURF-SNRPN upstream transcript is expressed already at meiosis. Several epigenetic factors (eg, MBD1 and MBD2 isoforms, MBD3L1, SUVH39H2, BRDT, and EZH2) are upregulated at specific stages of spermatogenesis, suggesting that they play an important role in the epigenetic reprogramming during spermatogenesis.

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References

OCarroll D, Scherthan H, Peters A, Opravil S, Haynes A, Laible G . Isolation and characterization of Suv39h2, a second histone H3 methyltransferase gene that displays testis-specific expression. Mol Cell Biol. 2000; 20(24):9423-33. PMC: 102198. DOI: 10.1128/MCB.20.24.9423-9433.2000. View

Feig C, Kirchhoff C, Ivell R, Naether O, Schulze W, Spiess A . A new paradigm for profiling testicular gene expression during normal and disturbed human spermatogenesis. Mol Hum Reprod. 2006; 13(1):33-43. DOI: 10.1093/molehr/gal097. View

Sasaki H, Matsui Y . Epigenetic events in mammalian germ-cell development: reprogramming and beyond. Nat Rev Genet. 2008; 9(2):129-40. DOI: 10.1038/nrg2295. View

Farber C, Gross S, Neesen J, Buiting K, Horsthemke B . Identification of a testis-specific gene (C15orf2) in the Prader-Willi syndrome region on chromosome 15. Genomics. 2000; 65(2):174-83. DOI: 10.1006/geno.2000.6158. View

Bosotti R, Locatelli G, Healy S, Scacheri E, Sartori L, Mercurio C . Cross platform microarray analysis for robust identification of differentially expressed genes. BMC Bioinformatics. 2007; 8 Suppl 1:S5. PMC: 1885857. DOI: 10.1186/1471-2105-8-S1-S5. View

Mapendano C, Kishino T, Miyazaki K, Kondo S, Yoshiura K, Hishikawa Y . Expression of the Snurf-Snrpn IC transcript in the oocyte and its putative role in the imprinting establishment of the mouse 7C imprinting domain. J Hum Genet. 2006; 51(3):236-243. DOI: 10.1007/s10038-005-0351-8. View

El-Maarri O, Buiting K, Peery E, Kroisel P, Balaban B, Wagner K . Maternal methylation imprints on human chromosome 15 are established during or after fertilization. Nat Genet. 2001; 27(3):341-4. DOI: 10.1038/85927. View

Spiess A, Feig C, Schulze W, Chalmel F, Cappallo-Obermann H, Primig M . Cross-platform gene expression signature of human spermatogenic failure reveals inflammatory-like response. Hum Reprod. 2007; 22(11):2936-46. DOI: 10.1093/humrep/dem292. View

Bhattacharya S, Ramchandani S, Cervoni N, Szyf M . A mammalian protein with specific demethylase activity for mCpG DNA. Nature. 1999; 397(6720):579-83. DOI: 10.1038/17533. View

10.

Farber C, Dittrich B, Buiting K, Horsthemke B . The chromosome 15 imprinting centre (IC) region has undergone multiple duplication events and contains an upstream exon of SNRPN that is deleted in all Angelman syndrome patients with an IC microdeletion. Hum Mol Genet. 1999; 8(2):337-43. DOI: 10.1093/hmg/8.2.337. View

11.

Shang E, Salazar G, Crowley T, Wang X, Lopez R, Wang X . Identification of unique, differentiation stage-specific patterns of expression of the bromodomain-containing genes Brd2, Brd3, Brd4, and Brdt in the mouse testis. Gene Expr Patterns. 2004; 4(5):513-9. DOI: 10.1016/j.modgep.2004.03.002. View

12.

Hendrich B, Bird A . Identification and characterization of a family of mammalian methyl-CpG binding proteins. Mol Cell Biol. 1998; 18(11):6538-47. PMC: 109239. DOI: 10.1128/MCB.18.11.6538. View

13.

Shemer R, Hershko A, Perk J, Mostoslavsky R, Tsuberi B, Cedar H . The imprinting box of the Prader-Willi/Angelman syndrome domain. Nat Genet. 2000; 26(4):440-3. DOI: 10.1038/82571. View

14.

Dittrich B, Buiting K, Korn B, Rickard S, Buxton J, Saitoh S . Imprint switching on human chromosome 15 may involve alternative transcripts of the SNRPN gene. Nat Genet. 1996; 14(2):163-70. DOI: 10.1038/ng1096-163. View

15.

Loukinov D, Pugacheva E, Vatolin S, Pack S, Moon H, Chernukhin I . BORIS, a novel male germ-line-specific protein associated with epigenetic reprogramming events, shares the same 11-zinc-finger domain with CTCF, the insulator protein involved in reading imprinting marks in the soma. Proc Natl Acad Sci U S A. 2002; 99(10):6806-11. PMC: 124484. DOI: 10.1073/pnas.092123699. View

16.

Chotalia M, Smallwood S, Ruf N, Dawson C, Lucifero D, Frontera M . Transcription is required for establishment of germline methylation marks at imprinted genes. Genes Dev. 2009; 23(1):105-17. PMC: 2632167. DOI: 10.1101/gad.495809. View

17.

Jiang C, Jin S, Lee D, Lan Z, Xu X, OConnor T . MBD3L1 and MBD3L2, two new proteins homologous to the methyl-CpG-binding proteins MBD2 and MBD3: characterization of MBD3L1 as a testis-specific transcriptional repressor. Genomics. 2002; 80(6):621-9. DOI: 10.1006/geno.2002.7001. View

18.

Ng H, Zhang Y, Hendrich B, Johnson C, Turner B, Erdjument-Bromage H . MBD2 is a transcriptional repressor belonging to the MeCP1 histone deacetylase complex. Nat Genet. 1999; 23(1):58-61. DOI: 10.1038/12659. View

19.

Horsthemke B, Wagstaff J . Mechanisms of imprinting of the Prader-Willi/Angelman region. Am J Med Genet A. 2008; 146A(16):2041-52. DOI: 10.1002/ajmg.a.32364. View

20.

Buiting K, Nazlican H, Galetzka D, Wawrzik M, Gross S, Horsthemke B . C15orf2 and a novel noncoding transcript from the Prader-Willi/Angelman syndrome region show monoallelic expression in fetal brain. Genomics. 2007; 89(5):588-95. DOI: 10.1016/j.ygeno.2006.12.008. View