Autonomous gene expression on the human inactive X chromosome

1980 ◽  
Vol 6 (3) ◽  
pp. 309-323 ◽  
Author(s):  
Brenda Kahan ◽  
Robert DeMars
Keyword(s):  
Gene Expression ◽  
X Chromosome ◽  
Inactive X Chromosome

scholarly journals BRCa1 participates in XIST RNa localization on inactive x chromosome

2019 ◽  
Vol 18 (2) ◽  
pp. 21-26
Author(s):  
E. A. Shestakova ◽  
T. A. Bogush
Keyword(s):  
Gene Expression ◽  
Cell Cycle ◽  
Confocal Microscopy ◽  
X Chromosome ◽  
Fluorescent Microscopy ◽  
S Phase ◽  
Immunofluorescent Staining ◽  
Heterochromatin Protein ◽  
Inactive X Chromosome ◽  
Xist Rna

Introduction . Inactive X chromosome (Xi) is associated with noncoding XIST RNA, series of proteins and contains multiple epigenetic modifications that altogether determine a silence of the most of X-linked genes. Recently the data were obtained that tumor suppressor BRCA1 is also associated with Xi. The purpose of this study was to reveal the colocalization of BRCA1 and XIST RNA and precise spatial organization on Xi with the high resolution of confocal microscopy.Materials and methods . The object of the study is IMR90hTERT diploid immortalized fibroblast cell line. For BRCA1 and XIST RNA colocalization analysis on Xi the method of fluorescent hybridization in situ associated with immunofluorescent cell staining (immunoFISH) and confocal microscopy were used. For BRCA1 and heterochromatin protein-1 colocalization study the method of double immunofluorescent staining and common fluorescent microscopy were applied. Results . The study using confocal fluorescent microscopy with higher resolution has demonstrated at first the colocalization of BRCA1 with XIST RNA region of Xi revealed with XIST RNA probes and with replicating Xi and autosomes revealed with BrdU in late S-phase of cell cycle. Altogether, the data obtained suggest the involvement of BRCA1 in the inhibition of gene expression on Xi due to the regulation of XIST RNA association with Xi. Moreover, according to the results of confocal microscopy, BRCA1 also colocalizes with replicating Xi and autosomes revealed with BrdU in late S-phase of cell cycle. This indicates a possible involvement of this protein in the replication of pericentromeric repeats in cellular chromosomes. Colocalization of BRCA1 with heterochromatin protein-1α presented in pericentromeric regions of all chromosomes supports this suggestion.Conclusions . Altogether, the data obtained in this study suggest the involvement of BRCA1 in the inhibition of gene expression on Xi due to the association with noncoding inhibiting XIST RNA and in replication of heterochromatin regions. 

The making of a Barr body: the mosaic of factors that eXIST on the mammalian inactive X chromosome

2016 ◽  
Vol 94 (1) ◽  
pp. 56-70 ◽  
Author(s):  
Thomas Dixon-McDougall ◽  
Carolyn Brown
Keyword(s):  
Gene Expression ◽  
X Chromosome ◽  
Current Knowledge ◽  
Pericentric Heterochromatin ◽  
Barr Body ◽  
Facultative Heterochromatin ◽  
Inactive X Chromosome ◽  
Non Coding Rna ◽  
Stable Maintenance ◽  
Long Non Coding Rna

During X-chromosome inactivation (XCI), nearly an entire X chromosome is permanently silenced and converted into a Barr body, providing dosage compensation for eutherians between the sexes. XCI is facilitated by the upregulation of the long non-coding RNA gene, XIST, which coats its chromosome of origin, recruits heterochromatin factors, and silences gene expression. During XCI, at least two distinct types of heterochromatin are established, and in this review we discuss the enrichment of facultative heterochromatin marks such as H3K27me3, H2AK119ub, and macroH2A as well as pericentric heterochromatin marks such as HP1, H3K9me3, and H4K20me3. The extremely stable maintenance of silencing is a product of reinforcing interactions within and between these domains. This paper “Xplores” the current knowledge of the pathways involved in XCI, how the pathways interact, and the gaps in our understanding that need to be filled.

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 X chromosome-dependent disruption of placental regulatory networks in hybrid dwarf hamsters

Genetics ◽  
2021 ◽  
Author(s):  
Thomas D Brekke ◽  
Emily C Moore ◽  
Shane C Campbell-Staton ◽  
Colin M Callahan ◽  
Zachary A Cheviron ◽  
...  
Keyword(s):  
Gene Expression ◽  
X Chromosome ◽  
Regulatory Networks ◽  
Mammalian Species ◽  
Strongly Correlated ◽  
Placental Development ◽  
Substitution Lines ◽  
Genome Wide ◽  
Highly Sensitive ◽  
First And Second Generation

AbstractEmbryonic development in mammals is highly sensitive to changes in gene expression within the placenta. The placenta is also highly enriched for genes showing parent-of-origin or imprinted expression, which is predicted to evolve rapidly in response to parental conflict. However, little is known about the evolution of placental gene expression, or if divergence of placental gene expression plays an important role in mammalian speciation. We used crosses between two species of dwarf hamsters (Phodopus sungorus and Phodopus campbelli) to examine the genetic and regulatory underpinnings of severe placental overgrowth in their hybrids. Using quantitative genetic mapping and mitochondrial substitution lines, we show that overgrowth of hybrid placentas was primarily caused by genetic differences on the maternally inherited P. sungorus X chromosome. Mitochondrial interactions did not contribute to abnormal hybrid placental development, and there was only weak correspondence between placental disruption and embryonic growth. Genome-wide analyses of placental transcriptomes from the parental species and first- and second-generation hybrids revealed a central group of co-expressed X-linked and autosomal genes that were highly enriched for maternally biased expression. Expression of this gene network was strongly correlated with placental size and showed widespread misexpression dependent on epistatic interactions with X-linked hybrid incompatibilities. Collectively, our results indicate that the X chromosome is likely to play a prominent role in the evolution of placental gene expression and the accumulation of hybrid developmental barriers between mammalian species.

Sign in / Sign up

Export Citation Format

Share Document