HP1γ links histone methylation marks to meiotic synapsis in mice

Abstract

SUMMARYDuring meiosis, specific histone modifications at pericentric heterochromatin (PCH), especially histone H3 tri-and dimethylation at lysine 9 (H3K9me3 and H3K9me2, respectively), are required for proper chromosome interactions. However, the molecular mechanism by which H3K9 methylation mediates the synapsis is not yet understood. We have generated a Cbx3-deficient mouse line and performed comparative analysis on Suv39h1/h2-, G9a-and Cbx3-deficient spermatocytes. This study revealed that H3K9me2 at PCH depended on Suv39h1/h2-mediated H3K9me3 and its recognition by the Cbx3 gene product HP1. We further found that centromere clustering and synapsis were commonly affected in G9a-and Cbx3-deficient spermatocytes. These genetic observations suggest that HP1/G9a-dependent PCH-mediated centromere clustering is an axis for proper chromosome interactions during meiotic prophase. We propose that the role of the HP1/G9a axis is to retain centromeric regions of unpaired homologous chromosomes in close alignment and facilitate progression of their pairing in early meiotic prophase. This study also reveals considerable plasticity in the interplay between different histone modifications and suggests that such stepwise and dynamic epigenetic modifications may play a pivotal role in meiosis.

Loss of Nucleolar Histone Chaperone NPM1 Triggers Rearrangement of Heterochromatin and Synergizes with a Deficiency in DNA Methyltransferase DNMT3A to Drive Ribosomal DNA Transcription

“…We observed HP1␥-NPM1 co-localization in the perinucleolar region, and interestingly, NPM1 was required for the efficient tethering of HP1␥ to the nucleolus. It should be pointed out that loss of HP1␥ function may negatively affect centromere clustering and cohesion processes (62)(63)(64). In fact, the loss of HP1␥ in Drosophila resulted in nucleolar deformation and fragmentation.…”

An epigenetic switch is crucial for spermatogonia to exit the undifferentiated state toward a Kit-positive identity

“…H3K9me2 is mainly associated with facultative heterochromatin, whereas H3K9me3 is observed at constitutive heterochromatin, particularly at pericentromeric heterochromatin (PH). In meiotic spermatogonia, both H3K9me2 and H3K9me3 reportedly are crucial for pairing of homologous chromosomes (Peters et al, 2001;Takada et al, 2011); and although H3K9, H3K27 and H4K20 modifications during the mitotic phase have been characterized histologically (Payne and Braun, 2006), their biological significance with respect to spermatogonial differentiation remains unclear.…”

HP-1γ Controls High-Affinity Antibody Response to T-Dependent Antigens

“…The cbx-3 (gene encoding HP-1γ) mutant mouse was generated by gene-trapping technology as described previously (10, 28). We found that cbx-3 − /− mice died perinatally.…”

“…In addition, HP-1γ has been found associated with both heterochromatin and euchromatin suggesting that it participates in transcriptional repression and activation, respectively (4, 8, 9). HP-1γ interacts with the methyl groups of H3K9 through the chromodomain (CD) and with the methyl transferase SUV39-H1 and other proteins through the chromoshadow domain (CSD) (2, 3, 10). Despite these crucial in vitro observations, it is not understood if and how HP-1γ contributes to the regulation of immunity in mammals in vivo .…”