scholarly journals SmcHD1 underlies the formation of H3K9me3 blocks on the inactive X chromosome in mice

2021 ◽  
Author(s):  
Takashi Sado ◽  
Saya Ichihara ◽  
Koji Nagao ◽  
Takehisa Sakaguchi ◽  
Chikashi Obuse
Keyword(s):  
X Chromosome ◽  
Critical Role ◽  
Underlying Mechanism ◽  
Wild Type ◽  
Embryonic Fibroblasts ◽  
Heterochromatin Formation ◽  
Epiblast Stem Cells ◽  
Epigenetic State ◽  
Inactive X Chromosome ◽  
Functional Deficiency

Stable silencing of the inactive X chromosome (Xi) in female mammals is critical for the development of embryos and their postnatal health. SmcHD1 is essential for stable silencing of the Xi, and its functional deficiency results in derepression of many X-inactivated genes. Although SmcHD1 has been suggested to play an important role in the formation of higher order chromatin structure of the Xi, the underlying mechanism is largely obscure. Here we explore the epigenetic state of the Xi in SmcHD1-deficient epiblast stem cells (EpiSCs) and mouse embryonic fibroblasts (MEFs) in comparison with their wild-type counterparts. The results suggest that SmcHD1 underlies the formation of H3K9me3-enriched blocks on the Xi, which, although the importance of H3K9me3 has been largely overlooked in mice, play a critical role in the establishment of the stably silenced state. We propose that the H3K9me3 blocks formed on the Xi facilitate robust heterochromatin formation in combination with H3K27me3, and the substantial loss of H3K9me3 caused by SmcHD1 deficiency leads to aberrant distribution of H3K27me3 on the Xi and derepression of X-inactivated genes.

scholarly journals Live Cell Imaging of the Nascent Inactive X Chromosome during the Early Differentiation Process of Naive ES Cells towards Epiblast Stem Cells

PLoS ONE ◽  
2014 ◽  
Vol 9 (12) ◽  
pp. e116109 ◽  
Author(s):  
Aurélia Guyochin ◽  
Sylvain Maenner ◽  
Erin Tsi-Jia Chu ◽  
Asma Hentati ◽  
Mikael Attia ◽  
...  
Keyword(s):  
Stem Cells ◽  
X Chromosome ◽  
Live Cell Imaging ◽  
Cell Imaging ◽  
Es Cells ◽  
Live Cell ◽  
Differentiation Process ◽  
Early Differentiation ◽  
Epiblast Stem Cells ◽  
Inactive X Chromosome

scholarly journals Loss of the Inactive X Chromosome and Replication of the Active X in BRCA1-Defective and Wild-type Breast Cancer Cells

2005 ◽  
Vol 65 (6) ◽  
pp. 2139-2146 ◽  
Author(s):  
Silvia M. Sirchia ◽  
Lisetta Ramoscelli ◽  
Francesca R. Grati ◽  
Floriana Barbera ◽  
Danila Coradini ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
X Chromosome ◽  
Breast Cancer Cells ◽  
Wild Type ◽  
Inactive X Chromosome

scholarly journals The Dual-Specificity Protein Phosphatase DUSP9/MKP-4 Is Essential for Placental Function but Is Not Required for Normal Embryonic Development

2005 ◽  
Vol 25 (18) ◽  
pp. 8323-8333 ◽  
Author(s):  
Graham R. Christie ◽  
David J. Williams ◽  
Fiona MacIsaac ◽  
Robin J. Dickinson ◽  
Ian Rosewell ◽  
...  
Keyword(s):  
Embryonic Development ◽  
X Chromosome ◽  
Critical Role ◽  
Physiological Role ◽  
Giant Cells ◽  
Mitogen Activated Protein Kinase ◽  
Wild Type ◽  
Placental Development ◽  
Dual Specificity ◽  
Dual Specificity Protein Phosphatase

ABSTRACT To elucidate the physiological role(s) of DUSP9 (dual-specificity phosphatase 9), also known as MKP-4 (mitogen-activated protein kinase [MAPK] phosphatase 4), the gene was deleted in mice. Crossing male chimeras with wild-type females resulted in heterozygous (DUSP9+/−) females. However, when these animals were crossed with wild-type (DUSP9+/y) males none of the progeny carried the targeted DUSP9 allele, indicating that both female heterozygous and male null (DUSP9−/y) animals die in utero. The DUSP9 gene is on the X chromosome, and this pattern of embryonic lethality is consistent with the selective inactivation of the paternal X chromosome in the extraembryonic tissues of the mouse, suggesting that DUSP9/MKP4 performs an essential function during placental development. Examination of embryos between 8 and 10.5 days postcoitum confirmed that lethality was due to a failure of labyrinth development, and this correlates exactly with the normal expression pattern of DUSP9/MKP-4 in the trophoblast giant cells and labyrinth of the placenta. Finally, when the placental defect was rescued, male null (DUSP9−/y) embryos developed to term, appeared normal, and were fertile. Our results indicate that DUSP9/MKP-4 is essential for placental organogenesis but is otherwise dispensable for mammalian embryonic development and highlights the critical role of dual-specificity MAPK phosphatases in the regulation of developmental outcomes in vertebrates.

scholarly journals The SAM Domains of Anks Family Proteins Are Critically Involved in Modulating the Degradation of EphA Receptors

2010 ◽  
Vol 30 (7) ◽  
pp. 1582-1592 ◽  
Author(s):  
Jieun Kim ◽  
Haeryung Lee ◽  
Yujin Kim ◽  
Sooyeon Yoo ◽  
Eunjeong Park ◽  
...  
Keyword(s):  
Potential Role ◽  
Critical Role ◽  
Dominant Negative ◽  
Eph Receptors ◽  
Wild Type ◽  
Embryonic Fibroblasts ◽  
Sam Domain ◽  
Ligand Stimulation ◽  
The Stability

ABSTRACT We recently reported that the phosphotyrosine-binding (PTB) domain of Anks family proteins binds to EphA8, thereby positively regulating EphA8-mediated signaling pathways. In the current study, we identified a potential role for the SAM domains of Anks family proteins in EphA signaling. We found that SAM domains of Anks family proteins directly bind to ubiquitin, suggesting that Anks proteins regulate the degradation of ubiquitinated EphA receptors. Consistent with the role of Cbl ubiquitin ligases in the degradation of Eph receptors, our results revealed that the ubiquitin ligase c-Cbl induced the ubiquitination and degradation of EphA8 upon ligand binding. Ubiquitinated EphA8 also bound to the SAM domains of Odin, a member of the Anks family proteins. More importantly, the overexpression of wild-type Odin protected EphA8 and EphA2 from undergoing degradation following ligand stimulation and promoted EphA-mediated inhibition of cell migration. In contrast, a SAM domain deletion mutant of Odin strongly impaired the function of endogenous Odin, suggesting that the mutant functions in a dominant-negative manner. An analysis of Odin-deficient primary embryonic fibroblasts indicated that Odin levels play a critical role in regulating the stability of EphA2 in response to ligand stimulation. Taken together, our studies suggest that the SAM domains of Anks family proteins play a pivotal role in enhancing the stability of EphA receptors by modulating the ubiquitination process.

scholarly journals Association of BRCA1 with the inactive X chromosome and XIST RNA

2004 ◽  
Vol 359 (1441) ◽  
pp. 123-128 ◽  
Author(s):  
Shridar Ganesan ◽  
Daniel P. Silver ◽  
Ronny Drapkin ◽  
Roger Greenberg ◽  
Jean Feunteun ◽  
...  
Keyword(s):  
X Chromosome ◽  
Fluorescent Protein ◽  
Wild Type ◽  
Cancer Syndrome ◽  
Suppressor Activity ◽  
Inactive X Chromosome ◽  
Xist Rna ◽  
Green Fluorescent ◽  
Cancer Suppression ◽  
Diploid Cells

Breast cancer, early onset 1 (BRCA1) encodes a nuclear protein that participates in breast and ovarian cancer suppression. The molecular basis for the gender and tissue specificity of the BRCA1 cancer syndrome is unknown. Recently, we observed that a fraction of BRCA1 in female cells is localized on the inactive X chromosome (Xi). Chromatin immunoprecipitation (ChIP) experiments have demonstrated that BRCA1 physically associates with Xi–specific transcript (XIST) RNA, a non–coding RNA known to coat Xi and to participate in the initiation of its inactivation during early embryogenesis. Cells lacking wild–type BRCA1 show abnormalities in Xi, including lack of proper XIST RNA localization. Reintroduction of wild–type, but not mutant, BRCA1 can correct this defect in XIST localization in these cells. Depletion of BRCA1 in female diploid cells led to a defect in proper XIST localization on Xi and in the development of normal Xi heterchromatic superstructure. Moreover, depletion of BRCA1 led to an increased likelihood of re–expression of a green fluorescent protein (GFP) reporter gene embedded on Xi. Taken together, these findings are consistent with a model in which BRCA1 function contributes to the maintenance of proper Xi heterochromatin superstructure. Although the data imply a novel gender–specific consequence of BRCA1 loss, the relevance of the BRCA1/Xi function to the tumour suppressor activity of BRCA1 remains unclear and needs to be tested.

scholarly journals Differential activation of the hprt gene on the inactive X chromosome in primary and transformed Chinese hamster cells.

1989 ◽  
Vol 9 (4) ◽  
pp. 1635-1641 ◽  
Author(s):  
S G Grant ◽  
R G Worton
Keyword(s):  
Cell Lines ◽  
X Chromosome ◽  
Gene Activation ◽  
Chinese Hamster ◽  
Fibroblast Cell ◽  
Dna Demethylation ◽  
Hprt Gene ◽  
Primary Fibroblast ◽  
Chinese Hamster Cells ◽  
Inactive X Chromosome

We have investigated the genetic activation of the hprt (hypoxanthine-guanine phosphoribosyltransferase) gene located on the inactive X chromosome in primary and transformed female diploid Chinese hamster cells after treatment with the DNA methylation inhibitor 5-azacytidine (5azaCR). Mutants deficient in HPRT were first selected by growth in 6-thioguanine from two primary fibroblast cell lines and from transformed lines derived from them. These HPRT- mutants were then treated with 5azaCR and plated in HAT (hypoxanthine-methotrexate-thymidine) medium to select for cells that had reexpressed the hprt gene on the inactive X chromosome. Contrary to previous results with primary human cells, 5azaCR was effective in activating the hprt gene in primary Chinese hamster fibroblasts at a low but reproducible frequency of 2 x 10(-6) to 7 x 10(-6). In comparison, the frequency in independently derived transformed lines varied from 1 x 10(-5) to 5 x 10(-3), consistently higher than in the nontransformed cells. This increase remained significant when the difference in growth rates between the primary and transformed lines was taken into account. Treatment with 5azaCR was also found to induce transformation in the primary cell lines but at a low frequency of 4 x 10(-7) to 8 x 10(-7), inconsistent with a two-step model of transformation followed by gene activation to explain the derepression of hprt in primary cells. Thus, these results indicate that upon transformation, the hprt gene on the inactive Chinese hamster X chromosome is rendered more susceptible to action by 5azaCR, consistent with a generalized DNA demethylation associated with the transformation event or with an increase in the instability of an underlying primary mechanism of X inactivation.

scholarly journals Transcriptome Analysis Provides Insights into the Mechanism of Astaxanthin Enrichment in a Mutant of the Ridgetail White Prawn Exopalaemon carinicauda

Genes ◽  
2021 ◽  
Vol 12 (5) ◽  
pp. 618
Author(s):  
Yue Jin ◽  
Shihao Li ◽  
Yang Yu ◽  
Chengsong Zhang ◽  
Xiaojun Zhang ◽  
...  
Keyword(s):  
Transcriptome Analysis ◽  
Underlying Mechanism ◽  
Biological Processes ◽  
Wild Type ◽  
Expression Levels ◽  
In The Wild ◽  
Cuticle Proteins ◽  
Apolipoprotein D ◽  
High Level ◽  
Lower Expression

A mutant of the ridgetail white prawn, which exhibited rare orange-red body color with a higher level of free astaxanthin (ASTX) concentration than that in the wild-type prawn, was obtained in our lab. In order to understand the underlying mechanism for the existence of a high level of free astaxanthin, transcriptome analysis was performed to identify the differentially expressed genes (DEGs) between the mutant and wild-type prawns. A total of 78,224 unigenes were obtained, and 1863 were identified as DEGs, in which 902 unigenes showed higher expression levels, while 961 unigenes presented lower expression levels in the mutant in comparison with the wild-type prawns. Based on Gene Ontology analysis and Kyoto Encyclopedia of Genes and Genomes analysis, as well as further investigation of annotated DEGs, we found that the biological processes related to astaxanthin binding, transport, and metabolism presented significant differences between the mutant and the wild-type prawns. Some genes related to these processes, including crustacyanin, apolipoprotein D (ApoD), cathepsin, and cuticle proteins, were identified as DEGs between the two types of prawns. These data may provide important information for us to understand the molecular mechanism of the existence of a high level of free astaxanthin in the prawn.

Sign in / Sign up

Export Citation Format

Share Document