Dosage compensation

About: Dosage compensation is a research topic. Over the lifetime, 1920 publications have been published within this topic receiving 124589 citations.

The Methylome of Vertebrate Sex Chromosomes.

Abstract: DNA methylation is a key epigenetic modification in vertebrate genomes known to be involved in the regulation of gene expression, X chromosome inactivation, genomic imprinting, chromatin structure, and control of transposable elements. DNA methylation is common to all eukaryote genomes, but we still lack a complete understanding of the variation in DNA methylation patterns on sex chromosomes and between the sexes in diverse species. To better understand sex chromosome DNA methylation patterns between different amniote vertebrates, we review literature that has analyzed the genome-wide distribution of DNA methylation in mammals and birds. In each system, we focus on DNA methylation patterns on the autosomes versus the sex chromosomes.

Genomic architecture constrained placental mammal X Chromosome evolution.

Abstract: Susumu Ohno proposed that the gene content of the mammalian X Chromosome should remain highly conserved due to dosage compensation. X Chromosome linkage (gene order) conservation is widespread in placental mammals but does not fall within the scope of Ohno's prediction and may be an indirect result of selection on gene content or selection against rearrangements that might disrupt X-Chromosome inactivation (XCI). Previous comparisons between the human and mouse X Chromosome sequences have suggested that although single-copy X Chromosome genes are conserved between species, most ampliconic genes were independently acquired. To better understand the evolutionary and functional constraints on X-linked gene content and linkage conservation in placental mammals, we aligned a new, high-quality, long-read X Chromosome reference assembly from the domestic cat (incorporating 19.3 Mb of targeted BAC clone sequence) to the pig, human, and mouse assemblies. A comprehensive analysis of annotated X-linked orthologs in public databases demonstrated that the majority of ampliconic gene families were present on the ancestral placental X Chromosome. We generated a domestic cat Hi-C contact map from an F1 domestic cat/Asian leopard cat hybrid and demonstrated the formation of the bipartite structure found in primate and rodent inactivated X Chromosomes. Conservation of gene order and recombination patterns is attributable to strong selective constraints on three-dimensional genomic architecture necessary for superloop formation. Species with rearranged X Chromosomes retain the ancestral order and relative spacing of loci critical for superloop formation during XCI, with compensatory inversions evolving to maintain these long-range physical interactions.

Further analysis on the male-specific lethal mutations that affect dosage compensation in Drosophila melanogaster.

Abstract: The male-specific lethal genes (msl) of D. melanogaster represent a set of genes whose functions are required for the specific X chromosome hypertranscription in males (dosage compensation). We have carried out the clonal analysis of one of those msl mutations: msl-3 b. Clones homozygous for msl-3 b are deleterious; this mutation presents cell autonomy and in the cases where msl clones appeared in sexually dimorphic regions (5th and 6th tergites) they do not show sexual transformation. Moreover, the lethal phase and the growth dynamics (measured by the protein content during larval growth) are the same for male larvae homozygous for one msl mutation (msl-1) or three msl mutations (msl-2 msl-1 mle), i.e. the msl mutations do not show additive effects. This paper considers the possible interactions between the msl genes that bring about dosage compensation.

New Insights into X-Chromosome Reactivation during Reprogramming to Pluripotency.

Abstract: Dosage compensation between the sexes results in one X chromosome being inactivated during female mammalian development. Chromosome-wide transcriptional silencing from the inactive X chromosome (Xi) in mammalian cells is erased in a process termed X-chromosome reactivation (XCR), which has emerged as a paradigm for studying the reversal of chromatin silencing. XCR is linked with germline development and induction of naive pluripotency in the epiblast, and also takes place upon reprogramming somatic cells to induced pluripotency. XCR depends on silencing of the long non-coding RNA (lncRNA) X inactive specific transcript (Xist) and is linked with the erasure of chromatin silencing. Over the past years, the advent of transcriptomics and epigenomics has provided new insights into the transcriptional and chromatin dynamics with which XCR takes place. However, multiple questions remain unanswered about how chromatin and transcription related processes enable XCR. Here, we review recent work on establishing the transcriptional and chromatin kinetics of XCR, as well as discuss a model by which transcription factors mediate XCR not only via Xist repression, but also by direct targeting of X-linked genes.

Evolution of the Larval Cuticle Proteins Coded by the Secondary Sex Chromosome Pair: X2 and Neo-Y of Drosophila miranda: II. Comparison at the Amino Acid Sequence Level

Abstract: The larval cuticle protein genes (Lcps) represent a multigene family located at the right arm of the metacentric autosome 2 (2R) inDrosophila melanogaster. Due to a chromosome fusion theLcp locus ofDrosophila miranda is situated on a pair of secondary sex chromosomes, theX2 andneo-Y chromosome. Comparing the DNA sequences fromD. miranda andD. melanogaster organization and the gene arrangement ofLcp1-Lcp4 are similar, although the intergene distances vary considerably. The greatest difference betweenLcp1 andLcp2 is due to the occurrence of a pseudogene inD. melanogaster which is not present inD. miranda. Thus the cluster of the fourLcp genes existed already before the separation of themelanogaster andobscura group. Intraspecific homogenizations of different cluster units must have occurred repeatedly between theLcp1/Lcp2 andLcp3/Lcp4 sequence types. The most obvious example is exon 2 of theLcp3 gene inD. miranda, which has been substituted by the corresponding section of theLcp4 gene rather recently. The homogenization must have occurred before the translocation which generated theneo-Y chromosome.Lcp3 ofD. melanogaster has therefore no orthologous partner inD. miranda. Rearrangements in the promoter regions of theD. miranda Lcp genes have generated new, potentially functional CAAT-box motifs. Since three of theLcp alleles on theneo-Y are not expressed andLcp3 is expressed only at a reduced level, it is suggestive to speculate that the rearrangements might be involved ascis-regulatory elements in the up-regulation of theX2-chromosomalLcp alleles, inDrosophila an essential process for dosage compensation. TheLcp genes on theneo-Y chromosome have accumulated more base substitutions than the corresponding alleles on theX2.