X chromosome regulation of autosomal gene expression in bovine blastocysts

In eutherian mammals, dosage compensation arose to balance X-linked gene expression between sexes and relatively to autosomal gene expression in the evolution of sex chromosomes. Dosage compensation occurs in early mammalian development and comprises X chromosome upregulation and inactivation that are tightly coordinated epigenetic processes. Despite a uniform principle of dosage compensation, mechanisms of X chromosome inactivation and upregulation demonstrate a significant variability depending on sex, developmental stage, cell type, individual, and mammalian species. The review focuses on relationships between X chromosome inactivation and upregulation in mammalian early development.

Download Full-text

Sex Chromosome Dosage Effects On Gene Expression In Humans

10.1101/137752 ◽

2017 ◽

Cited By ~ 2

Author(s):

Armin Raznahan ◽

Neelroop Parikshak ◽

Vijayendran Chandran ◽

Jonathan Blumenthal ◽

Liv Clasen ◽

...

Keyword(s):

Gene Expression ◽

Sex Differences ◽

X Chromosome ◽

Gene Networks ◽

Sex Chromosome ◽

Autosomal Gene ◽

Expression Data ◽

Systematic Map ◽

Genome Wide ◽

Genome Wide Expression

ABSTRACTA fundamental question in the biology of sex-differences has eluded direct study in humans: how does sex chromosome dosage (SCD) shape genome function? To address this, we developed a systematic map of SCD effects on gene function by analyzing genome-wide expression data in humans with diverse sex chromosome aneuploidies (XO, XXX, XXY, XYY, XXYY). For sex chromosomes, we demonstrate a pattern of obligate dosage sensitivity amongst evolutionarily preserved X-Y homologs, and update prevailing theoretical models for SCD compensation by detecting X-linked genes whose expression increases with decreasing X- and/or Y-chromosome dosage. We further show that SCD-sensitive sex chromosome genes regulate specific co-expression networks of SCD-sensitive autosomal genes with critical cellular functions and a demonstrable potential to mediate previously documented SCD effects on disease. Our findings detail wide-ranging effects of SCD on genome function with implications for human phenotypic variation.SIGNIFICANCE STATEMENTSex chromosome dosage (SCD) effects on human gene expression are central to the biology of sex differences and sex chromosome aneuploidy syndromes, but challenging to study given the co-segregation of SCD and gonadal status. We address this obstacle by systematically modelling SCD effects on genome wide expression data from a large and rare cohort of individuals with diverse SCDs (XO, XX, XXX, XXXX, XY, XXY, XYY, XXYY, XXXXY). Our findings update current models of sex chromosome biology by (i) pinpointing a core set of X- and Y-linked genes with “obligate” SCD sensitivity, (ii) discovering several non-canonical modes of X-chromosome dosage compensation, and (iii) dissecting complex regulatory effects of X-chromosome dosage on large autosomal gene networks with key roles in cellular functioning.

Download Full-text

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

Genetics ◽

10.1093/genetics/iyab043 ◽

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.

Download Full-text

Study of Dosage Compensation in Drosophila

Genetics ◽

10.1093/genetics/165.3.1167 ◽

2003 ◽

Vol 165 (3) ◽

pp. 1167-1181

Author(s):

Pei-Wen Chiang ◽

David M Kurnit

Keyword(s):

Gene Expression ◽

X Chromosome ◽

Dosage Compensation ◽

Qpcr Assay ◽

Male And Female ◽

Multiple Genes ◽

Chromosomal Changes ◽

Regulatory Effects

Abstract Using a sensitive RT-QPCR assay, we analyzed the regulatory effects of sex and different dosage compensation mutations in Drosophila. To validate the assay, we showed that regulation for several genes indeed varied with the number of functional copies of that gene. We then confirmed that dosage compensation occurred for most genes we examined in male and female flies. Finally, we examined the effects on regulation of several genes in the MSL pathway, presumed to be involved in sex-dependent determination of regulation. Rather than seeing global alterations of either X chromosomal or autosomal genes, regulation of genes on either the X chromosome or the autosomes could be elevated, depressed, or unaltered between sexes in unpredictable ways for the various MSL mutations. Relative dosage for a given gene between the sexes could vary at different developmental times. Autosomal genes often showed deranged regulatory levels, indicating they were in pathways perturbed by X chromosomal changes. As exemplified by the BR-C locus and its dependent Sgs genes, multiple genes in a given pathway could exhibit coordinate regulatory modulation. The variegated pattern shown for expression of both X chromosomal and autosomal loci underscores the complexity of gene expression so that the phenotype of MSL mutations does not reflect only simple perturbations of genes on the X chromosome.

Download Full-text

Autonomous gene expression on the human inactive X chromosome

Somatic Cell Genetics ◽

10.1007/bf01542785 ◽

1980 ◽

Vol 6 (3) ◽

pp. 309-323 ◽

Cited By ~ 16

Author(s):

Brenda Kahan ◽

Robert DeMars

Keyword(s):

Gene Expression ◽

X Chromosome ◽

Inactive X Chromosome

Download Full-text

Sex and death: from cell fate specification to dynamic control of X-chromosome structure and gene expression

Molecular Biology of the Cell ◽

10.1091/mbc.e18-06-0397 ◽

2018 ◽

Vol 29 (22) ◽

pp. 2616-2621 ◽

Cited By ~ 4

Author(s):

Barbara J. Meyer

Keyword(s):

Gene Expression ◽

Cell Fate ◽

X Chromosome ◽

Chromosome Structure ◽

Dynamic Control ◽

Three Dimensional ◽

X Chromosomes ◽

Meiotic Chromosomes ◽

The Difference ◽

Developmental Decision

Determining sex is a binary developmental decision that most metazoans must make. Like many organisms, Caenorhabditis elegans specifies sex (XO male or XX hermaphrodite) by tallying X-chromosome number. We dissected this precise counting mechanism to determine how tiny differences in concentrations of signals are translated into dramatically different developmental fates. Determining sex by counting chromosomes solved one problem but created another—an imbalance in X gene products. We found that nematodes compensate for the difference in X-chromosome dose between sexes by reducing transcription from both hermaphrodite X chromosomes. In a surprising feat of evolution, X-chromosome regulation is functionally related to a structural problem of all mitotic and meiotic chromosomes: achieving ordered compaction of chromosomes before segregation. We showed the dosage compensation complex is a condensin complex that imposes a specific three-dimensional architecture onto hermaphrodite X chromosomes. It also triggers enrichment of histone modification H4K20me1. We discovered the machinery and mechanism underlying H4K20me1 enrichment and demonstrated its pivotal role in regulating higher-order X-chromosome structure and gene expression.

Download Full-text

Random X Inactivation and Extensive Mosaicism in Human Placenta Revealed by Analysis of Allele-Specific Gene Expression along the X Chromosome

PLoS ONE ◽

10.1371/journal.pone.0010947 ◽

2010 ◽

Vol 5 (6) ◽

pp. e10947 ◽

Cited By ~ 81

Author(s):

Joana Carvalho Moreira de Mello ◽

Érica Sara Souza de Araújo ◽

Raquel Stabellini ◽

Ana Maria Fraga ◽

Jorge Estefano Santana de Souza ◽

...

Keyword(s):

Gene Expression ◽

X Chromosome ◽

Human Placenta ◽

X Inactivation ◽

Specific Gene ◽

Specific Gene Expression ◽

Allele Specific

Download Full-text

BRCa1 participates in XIST RNa localization on inactive x chromosome

Russian Journal of Biotherapy ◽

10.17650/1726-9784-2019-18-2-21-26 ◽

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.

Download Full-text

Drosophila Male-Specific Lethal 2 Protein Controls Sex-Specific Expression of the roX Genes

Genetics ◽

10.1093/genetics/166.4.1825 ◽

2004 ◽

Vol 166 (4) ◽

pp. 1825-1832 ◽

Cited By ~ 1

Author(s):

Barbara P Rattner ◽

Victoria H Meller

Keyword(s):

Gene Expression ◽

Transcriptional Regulation ◽

X Chromosome ◽

Specific Expression ◽

Linked Gene ◽

Male And Female ◽

Male Specific Lethal ◽

Msl Complex ◽

Male Specific ◽

Rox Rna

Abstract The MSL complex of Drosophila upregulates transcription of the male X chromosome, equalizing male and female X-linked gene expression. Five male-specific lethal proteins and at least one of the two noncoding roX RNAs are essential for this process. The roX RNAs are required for the localization of MSL complexes to the X chromosome. Although the mechanisms directing targeting remain speculative, the ratio of MSL protein to roX RNA influences localization of the complex. We examine the transcriptional regulation of the roX genes and show that MSL2 controls male-specific roX expression in the absence of any other MSL protein. We propose that this mechanism maintains a stable MSL/roX ratio that is favorable for localization of the complex to the X chromosome.

Download Full-text