HP1γ function is required for male germ cell survival and spermatogenesis

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

doi:10.1186/1756-8935-3-9

Cited by 59 publications

(36 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In biochemical assays HP1 isotypes are interchangeable and can form heterodimers (Nielsen et al 2001). Despite this they are not functionally redundant as evidenced by their different mutant phenotypes (Aucott et al 2008;Brown et al 2010;Singh 2010). Immuno-localization studies have shown that HP1α and HP1β are enriched within constitutive heterochromatin, while HP1γ has a more euchromatic distribution (Minc et al 1999).…”

Section: Mammalian Hp1 Proteins and Heterochromatin-like Complexesmentioning

confidence: 99%

Heterochromatin and the molecular mechanisms of ‘parent-of-origin’ effects in animals

Singh

2016

J Biosci

Self Cite

View full text Add to dashboard Cite

Twenty five years ago it was proposed that conserved components of constitutive heterochromatin assemble heterochromatinlike complexes in euchromatin and this could provide a general mechanism for regulating heritable (cell-to-cell) changes in gene expressibility. As a special case, differences in the assembly of heterochromatin-like complexes on homologous chromosomes might also regulate the parent-of-origin-dependent gene expression observed in placental mammals. Here, the progress made in the intervening period with emphasis on the role of heterochromatin and heterochromatin-like complexes in parent-of-origin effects in animals is reviewed.[Singh PB 2016 Heterochromatin and the molecular mechanisms of 'parent-of-origin' effects in animals. J. Biosci.] http://www.ias.ac.in/jbiosci J. Biosci. * Indian Academy of Sciences DOI: 10.1007/s12038-016-9650-9Keywords. Epigenetics; genomic imprinting; heterochromatin; HP1; KRAB-ZFP Abbreviations used: 5hmC, 5-hydroxymethylcytosine; 5mC, 5-methylcytosine; ADD, ATRX-DNMT3-DNMT3L domain; ATRX, Alpha Thalassemia/Mental Retardation Syndrome X-Linked; CAF-1, chromatin assembly factor 1; CD, chromodomain; CE, controlling element; CF, chromocenter formation; CGIs, CpG islands; CSD, chromo shadow domain; DamID, DNA adenine methyltransferase identification; DAXX, Death Domain associated protein; DNMT1, maintenance DNA methyltransferase 1; DNMT3A, de novo DNA methyltransferase 3A; DNMT3B, de novo DNA methyltransferase 3B; DNMT3L, DNA methyltransferase 3L; ES, embryonic stem; G9a, K9H3 HMTase; GLP, G9a-like protein K9H3 HMTase; gDMRs, germline differentially methylated regions; H3K9me2, di-methylated lysine 9 on histone H3; H3K9me3, tri-methylated lysine 9 on histone H3; H3S10P, phosphorylation of serine 10 on histone H3; H4K20me3, tri-methylated lysine 20 on histone

show abstract

Section: Mammalian Hp1 Proteins and Heterochromatin-like Complexesmentioning

confidence: 99%

Heterochromatin and the molecular mechanisms of ‘parent-of-origin’ effects in animals

Singh

2016

J Biosci

Self Cite

View full text Add to dashboard Cite

show abstract

“…15 More specifically, Cbx3 has been documented to negatively regulate adipocyte differentiation from preadipocyte cells and is required for male germ cell survival and spermatogenesis. 16 Another study also suggested Cbx3 plays an important role in the epigenetic regulation of both cell differentiation and cancer development. 17 However, little is known about the functional involvement of Cbx3 protein in SMC differentiation from stem/progenitor cells and cardiovascular system development.…”

mentioning

confidence: 99%

Chromobox Protein Homolog 3 Is Essential for Stem Cell Differentiation to Smooth Muscles In Vitro and in Embryonic Arteriogenesis

Xiao

Wang

Yin

et al. 2011

ATVB

View full text Add to dashboard Cite

Objective-Smooth muscle cell (SMC) differentiation is a critical process during cardiovascular formation and development, but the underlying molecular mechanism remains unclear. Methods and Results-Here we demonstrated that chromobox protein homolog 3 (Cbx3) is crucial for SMC differentiation from stem cells and that the chromodomain and chromoshadow domain of Cbx3 are responsible for Cbx3-induced SMC differentiation. Moreover, we identified that 4 amino acids (165 to 168) within the chromoshadow domain of Cbx3 are key elements for Cbx3 interaction with Dia-1-and Cbx3-induced SMC differentiation. Mechanistically, we found that Cbx3 mediates SMC differentiation through modulating serum response factor (SRF) recruitment to the promoters of SMC genes, in which the interaction between Cbx3 and Dia-1/SRF plays a crucial role in this process. Moreover, our in vivo study demonstrated that the misexpression of Cbx3 within neural crest cells of chick embryos resulted in the death of chick embryos at early stages because of the maldevelopment of branchial arch arteries. Key Words: chromobox protein homolog 3 Ⅲ arteriogenesis Ⅲ chick embryos Ⅲ smooth muscle cells Ⅲ stem cells A major achievement in the past decade has been made in the field of cardiovascular research and stem cell biology, in which embryonic stem (ES) cells were reported to differentiate into vascular cells, including vascular smooth muscle cells (SMCs) 1,2 and endothelial cells, [3][4][5][6][7][8] representing a potential unlimited cell source for vascular tissue repair and constructing engineered vasculatures. Moreover, growing evidence suggests that vascular stem/progenitor cells play a major role in various cardiovascular diseases, including atherosclerosis and angioplasty-induced restenosis. 9 -12 Cell differentiation from stem/progenitor cells is a multistep process marked by progressive silencing of pluripotent gene expression and the activation of specific cell-lineage gene expression through mechanisms likely to involve heterochromatin and associated proteins. As a major heterochromatinassociated protein, the protein encoded by the chromobox protein homolog gene (Cbx) could be an ideal candidate for controlling terminal cell differentiation from stem cells. Conclusion-OurIndeed, previous studies have suggested the involvement of Cbx3 (encoding the heterochromatin protein [HP]-1␥ protein) and its close family members Cbx1 and Cbx5 (encoding HP1␤ and ␣, respectively) in cell lineage differentiation. By interacting with transcriptional intermediary factor 1␤, Cbx proteins have been reported to be involved in retinoic-acidinduced primitive endoderm differentiation. 13,14 Further study from the same research group suggested that although all 3 Cbx proteins are found in both eu-and heterochromatin, they display a clear specificity of interaction and localization when associated with specific partners. This strongly indicates that different Cbx isotypes play specific nonredundant functions during cell differentiation. 15 More specifically, Cbx3 has been...

show abstract

“…9 Similarly, knockout of CBX5, the gene that encodes for HP1a has no apparent phenotype. 10,11 Consistent with these phenotypes, WRN-/-mice, unlike humans, have no phenotype. 12 But given the results of Zhang et al in human MSC's, a Werner's syndrome-like phenotype might have been expected for both SUV39H1 and CBX5 null mutants.…”

Section: Introductionmentioning

confidence: 54%

Stem Cell Depletion by Global Disorganization of the H3K9me3 Epigenetic Marker in Aging

Mendelsohn

Larrick

2015

Rejuvenation Research

View full text Add to dashboard Cite

Epigenomic change and stem cell exhaustion are two of the hallmarks of aging. Accumulation of molecular damage is thought to underlie aging, but the precise molecular composition of the damage remains controversial. That some aging phenotypes, especially those that result from impaired stem cell function, are reversible suggest that such "damage" is repairable. Evidence is accumulating that dysfunction in aging stem cells results from increasing, albeit, subtle disorganization of the epigenome over time. Zhang et al. (2015) report that decreasing levels of WRN, Werner's syndrome (WS) helicase, with increasing age results in loss of heterochromatin marks in mesenchymal stem cells (MSCs) and correlates with an increased rate of cellular senescence. Although WRN plays a role in DNA repair, WRN exerted its effects on aging via maintaining heterochromatin, evidenced by reduced levels of interacting chromatin regulators heterochromatin protein 1α (HP1α), suppressor of variegation 3-9 homolog 1 (SUV39H1), and lamina-associated polypeptide 2β (LAP2β) as well as modified histone H3K9me3. Reducing expression of chromatin modeling co-factors SUV39H1 or HP1α in wild-type MSCs recapitulates the phenotype of WRN deficiency, resulting in reduced H3K9me3 levels and increased senescence without induction of markers of DNA damage, suggesting that chromatin disorganization and not DNA damage is responsible for the pathology of WS during aging in animals. Ectopic expression of HP1α restored H3K9me3 levels and repressed senescence in WRN-deficient MSCs. That HP1α can also suppress senescence in Hutchinson-Gilford progeria syndrome (HGPS) and extend life span in flies when over-expressed suggests that HP1α and H3K9me3 play conserved roles in maintenance of cell state. H3K9me3 levels are dynamic and expected to be potentially responsive to manipulation by extrinsic factors. Recent reports that migration inhibitory factor (MIF) or periodic fasting rejuvenate old MSCs provide the opportunity to link intrinsic and extrinsic mechanisms of aging in novel and potentially medically important ways and may lead to anti-aging treatments that reorganize the epigenome to rejuvenate cells and tissues.

show abstract

HP1γ function is required for male germ cell survival and spermatogenesis

Cited by 59 publications

References 30 publications

Heterochromatin and the molecular mechanisms of ‘parent-of-origin’ effects in animals

Heterochromatin and the molecular mechanisms of ‘parent-of-origin’ effects in animals

Chromobox Protein Homolog 3 Is Essential for Stem Cell Differentiation to Smooth Muscles In Vitro and in Embryonic Arteriogenesis

Stem Cell Depletion by Global Disorganization of the H3K9me3 Epigenetic Marker in Aging

Contact Info

Product

Resources

About