HP1gamma function is required for male germ cell survival and spermatogenesis

Jeremy P Brown, Jörn Bullwinkel, Bettina Baron-Lühr, Mustafa Billur, Philipp Schneider, Heinz Winking, Prim B Singh

Research output: Contribution to journalArticle

38 Citations (Scopus)

Abstract

BACKGROUND: HP1 proteins are conserved components of eukaryotic constitutive heterochromatin. In mammals, there are three genes that encode HP1-like proteins, termed HP1alpha, HP1beta and HP1gamma, which have a high degree of homology This paper describes for the first time, to our knowledge, the physiological function of HP1gamma using a gene-targeted mouse.

RESULTS: While targeting the Cbx3 gene (encoding the HP1gamma protein) with a conditional targeting vector, we generated a hypomorphic allele (Cbx3hypo), which resulted in much reduced (barely detectable) levels of HP1gamma protein. Homozygotes for the hypomorphic allele (Cbx3hypo/hypo) are rare, with only 1% of Cbx3hypo/hypo animals reaching adulthood. Adult males exhibit a severe hypogonadism that is associated with a loss of germ cells, with some seminiferous tubules retaining only the supporting Sertoli cells (Sertoli cell-only phenotype). The percentage of seminiferous tubules that are positive for L1 ORF1 protein (ORF1p) in Cbx3hypo/hypo testes is greater than that for wild-type testes, indicating that L1 retrotransposon silencing is reversed, leading to ectopic expression of ORF1p in Cbx3hypo/hypo germ cells.

CONCLUSIONS: The Cbx3 gene product (the HP1gamma protein) has a non-redundant function during spermatogenesis that cannot be compensated for by the other two HP1 isotypes. The Cbx3hypo/hypo spermatogenesis defect is similar to that found in Miwi2 and Dnmt3L mutants. The Cbx3 gene-targeted mice generated in this study provide an appropriate model for the study of HP1gamma in transposon silencing and parental imprinting.

Original languageEnglish
Pages (from-to)9
JournalEpigenetics and Chromatin
Volume3
Issue number1
DOIs
Publication statusPublished - Apr 27 2010

Fingerprint

Spermatogenesis
Germ Cells
Cell Survival
Proteins
Seminiferous Tubules
Sertoli Cells
Testis
Alleles
Genes
Genomic Imprinting
Retroelements
Hypogonadism
Gene Targeting
Heterochromatin
Homozygote
Mammals
Phenotype

Keywords

  • Journal Article

Cite this

Brown, J. P., Bullwinkel, J., Baron-Lühr, B., Billur, M., Schneider, P., Winking, H., & Singh, P. B. (2010). HP1gamma function is required for male germ cell survival and spermatogenesis. Epigenetics and Chromatin, 3(1), 9. https://doi.org/10.1186/1756-8935-3-9

HP1gamma function is required for male germ cell survival and spermatogenesis. / Brown, Jeremy P; Bullwinkel, Jörn; Baron-Lühr, Bettina; Billur, Mustafa; Schneider, Philipp; Winking, Heinz; Singh, Prim B.

In: Epigenetics and Chromatin, Vol. 3, No. 1, 27.04.2010, p. 9.

Research output: Contribution to journalArticle

Brown, JP, Bullwinkel, J, Baron-Lühr, B, Billur, M, Schneider, P, Winking, H & Singh, PB 2010, 'HP1gamma function is required for male germ cell survival and spermatogenesis', Epigenetics and Chromatin, vol. 3, no. 1, pp. 9. https://doi.org/10.1186/1756-8935-3-9
Brown JP, Bullwinkel J, Baron-Lühr B, Billur M, Schneider P, Winking H et al. HP1gamma function is required for male germ cell survival and spermatogenesis. Epigenetics and Chromatin. 2010 Apr 27;3(1):9. https://doi.org/10.1186/1756-8935-3-9
Brown, Jeremy P ; Bullwinkel, Jörn ; Baron-Lühr, Bettina ; Billur, Mustafa ; Schneider, Philipp ; Winking, Heinz ; Singh, Prim B. / HP1gamma function is required for male germ cell survival and spermatogenesis. In: Epigenetics and Chromatin. 2010 ; Vol. 3, No. 1. pp. 9.
@article{2fdb7770e7b24af4b75d468036b4eff7,
title = "HP1gamma function is required for male germ cell survival and spermatogenesis",
abstract = "BACKGROUND: HP1 proteins are conserved components of eukaryotic constitutive heterochromatin. In mammals, there are three genes that encode HP1-like proteins, termed HP1alpha, HP1beta and HP1gamma, which have a high degree of homology This paper describes for the first time, to our knowledge, the physiological function of HP1gamma using a gene-targeted mouse.RESULTS: While targeting the Cbx3 gene (encoding the HP1gamma protein) with a conditional targeting vector, we generated a hypomorphic allele (Cbx3hypo), which resulted in much reduced (barely detectable) levels of HP1gamma protein. Homozygotes for the hypomorphic allele (Cbx3hypo/hypo) are rare, with only 1{\%} of Cbx3hypo/hypo animals reaching adulthood. Adult males exhibit a severe hypogonadism that is associated with a loss of germ cells, with some seminiferous tubules retaining only the supporting Sertoli cells (Sertoli cell-only phenotype). The percentage of seminiferous tubules that are positive for L1 ORF1 protein (ORF1p) in Cbx3hypo/hypo testes is greater than that for wild-type testes, indicating that L1 retrotransposon silencing is reversed, leading to ectopic expression of ORF1p in Cbx3hypo/hypo germ cells.CONCLUSIONS: The Cbx3 gene product (the HP1gamma protein) has a non-redundant function during spermatogenesis that cannot be compensated for by the other two HP1 isotypes. The Cbx3hypo/hypo spermatogenesis defect is similar to that found in Miwi2 and Dnmt3L mutants. The Cbx3 gene-targeted mice generated in this study provide an appropriate model for the study of HP1gamma in transposon silencing and parental imprinting.",
keywords = "Journal Article",
author = "Brown, {Jeremy P} and J{\"o}rn Bullwinkel and Bettina Baron-L{\"u}hr and Mustafa Billur and Philipp Schneider and Heinz Winking and Singh, {Prim B}",
year = "2010",
month = "4",
day = "27",
doi = "10.1186/1756-8935-3-9",
language = "English",
volume = "3",
pages = "9",
journal = "Epigenetics and Chromatin",
issn = "1756-8935",
publisher = "BioMed Central",
number = "1",

}

TY - JOUR

T1 - HP1gamma function is required for male germ cell survival and spermatogenesis

AU - Brown, Jeremy P

AU - Bullwinkel, Jörn

AU - Baron-Lühr, Bettina

AU - Billur, Mustafa

AU - Schneider, Philipp

AU - Winking, Heinz

AU - Singh, Prim B

PY - 2010/4/27

Y1 - 2010/4/27

N2 - BACKGROUND: HP1 proteins are conserved components of eukaryotic constitutive heterochromatin. In mammals, there are three genes that encode HP1-like proteins, termed HP1alpha, HP1beta and HP1gamma, which have a high degree of homology This paper describes for the first time, to our knowledge, the physiological function of HP1gamma using a gene-targeted mouse.RESULTS: While targeting the Cbx3 gene (encoding the HP1gamma protein) with a conditional targeting vector, we generated a hypomorphic allele (Cbx3hypo), which resulted in much reduced (barely detectable) levels of HP1gamma protein. Homozygotes for the hypomorphic allele (Cbx3hypo/hypo) are rare, with only 1% of Cbx3hypo/hypo animals reaching adulthood. Adult males exhibit a severe hypogonadism that is associated with a loss of germ cells, with some seminiferous tubules retaining only the supporting Sertoli cells (Sertoli cell-only phenotype). The percentage of seminiferous tubules that are positive for L1 ORF1 protein (ORF1p) in Cbx3hypo/hypo testes is greater than that for wild-type testes, indicating that L1 retrotransposon silencing is reversed, leading to ectopic expression of ORF1p in Cbx3hypo/hypo germ cells.CONCLUSIONS: The Cbx3 gene product (the HP1gamma protein) has a non-redundant function during spermatogenesis that cannot be compensated for by the other two HP1 isotypes. The Cbx3hypo/hypo spermatogenesis defect is similar to that found in Miwi2 and Dnmt3L mutants. The Cbx3 gene-targeted mice generated in this study provide an appropriate model for the study of HP1gamma in transposon silencing and parental imprinting.

AB - BACKGROUND: HP1 proteins are conserved components of eukaryotic constitutive heterochromatin. In mammals, there are three genes that encode HP1-like proteins, termed HP1alpha, HP1beta and HP1gamma, which have a high degree of homology This paper describes for the first time, to our knowledge, the physiological function of HP1gamma using a gene-targeted mouse.RESULTS: While targeting the Cbx3 gene (encoding the HP1gamma protein) with a conditional targeting vector, we generated a hypomorphic allele (Cbx3hypo), which resulted in much reduced (barely detectable) levels of HP1gamma protein. Homozygotes for the hypomorphic allele (Cbx3hypo/hypo) are rare, with only 1% of Cbx3hypo/hypo animals reaching adulthood. Adult males exhibit a severe hypogonadism that is associated with a loss of germ cells, with some seminiferous tubules retaining only the supporting Sertoli cells (Sertoli cell-only phenotype). The percentage of seminiferous tubules that are positive for L1 ORF1 protein (ORF1p) in Cbx3hypo/hypo testes is greater than that for wild-type testes, indicating that L1 retrotransposon silencing is reversed, leading to ectopic expression of ORF1p in Cbx3hypo/hypo germ cells.CONCLUSIONS: The Cbx3 gene product (the HP1gamma protein) has a non-redundant function during spermatogenesis that cannot be compensated for by the other two HP1 isotypes. The Cbx3hypo/hypo spermatogenesis defect is similar to that found in Miwi2 and Dnmt3L mutants. The Cbx3 gene-targeted mice generated in this study provide an appropriate model for the study of HP1gamma in transposon silencing and parental imprinting.

KW - Journal Article

U2 - 10.1186/1756-8935-3-9

DO - 10.1186/1756-8935-3-9

M3 - Article

VL - 3

SP - 9

JO - Epigenetics and Chromatin

JF - Epigenetics and Chromatin

SN - 1756-8935

IS - 1

ER -