Dosage compensation

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

Dosage compensation in mammals: why does a gene on the inactive X yield less product than one on the active X?

Abstract: An expressed gene on the inactive mammalian X chromosome yields less product than the same gene on the active X. Characteristics of the inactive X which might be responsible for this are late replication, chromatin clumping, and altered patterns of DNA methylation. If an expressed gene on the inactive X is not replicated until late in S, it will be present in two copies for a shorter fraction of the cell cycle than its early replicating homologue and therefore yield less product. Alternatively, transcription may be slowed by a microenvironment of highly condensed chromatin or by an abnormal pattern of methylation of the DNA template. Experiments are proposed by which to test these and related hypotheses.

Sex chromosome evolution of papaya: Dynamic structural and expression changes and identification of associated traits

Abstract: Carica papaya is a fruit crop with primitive sex chromosomes. Much work has already been done on the sex chromosomes, including whole genome sequencing, high-density genetic mapping, sequencing of the sex determining region (SDR) of the sex chromosomes, and detailed annotations of the genes located in the SDR. Previous studies determined that the sex chromosomes are approximately 7 million years old and that they have undergone many chromosomal changes, including two major inversions. The SDR spans 8.1 megabases (Mb) on the Y chromosome and 3.5 Mb on the corresponding region of the X chromosome. Papaya is also fruit crop with a short generation time and can flower in as little as 9 months and a well pollinated fruit can produce approximately 1000 seeds. These features makes papaya an ideal organism to study sex chromosome evolution and traits associated with the sex chromosomes. Papaya as a model organism Carica papaya is ideal for studying fruit tree genomics. It is a trioecious tropical subtropical crop tree that can reach maturity in as little as 3-8 months and once flowering has commenced, the tree continues to flower throughout the year. Each tree produces 75-300 pounds of fruit per year with each fruit containing upwards of 1000 seeds per fruit. The male, female, and hermaphrodite flowers are readily distinguished from one another and the sex specific organs are prominent. This allows for easily controlled crosses. This characteristic, in addition to the short generation time and high seed count makes the creation of mapping populations feasible, unlike fruit trees that take years to mature and produce only a few seeds per fruit. 1 Parts of this chapter appear in its entirety in Han. J., R. Ming. 2013 Molecular genetic mapping of papaya. In: R. Ming and P. Moore (eds.) Genetics and Genomics of Papaya. pp. 143-165. Springer, Heidelberg, Germany. This chapter is reprinted with permissions from the publisher. 2 Papaya is trioecious with sex type controlled by a pair of incipient sex chromosomes that are approximately 7 million years old (Wang et al., 2012); females are XX, males XY, and hermaphrodites have a modified Y chromosome and are designated as XY h (Ming R. et al,. 2001; Ming R. et al., 2007). The genome size is relatively small at 442.5 Mb (Gschwend et al., 2012) and has a small number of chromosomes (2n = 18). The sex determining region of the sex chromosomes is relatively small and contains the genes that not only control sex type, but also many genes controlling traits associated with the different sex types, including peduncle length and branch number. This region comprises approximately 10% (3.5 Mb) and 13% (8.1 Mb) of the X and Y chromosome, respectively (Liu et al., 2004; Wang et al., 2012). There is little genome heterozygosity due to extensive inbreeding. Papaya is readily transformed via microprojectile bombardment (Fitch et al., 1992). These characteristics make it ideal for studying the dynamic changes involved in sex chromosome evolution, including gene degeneration, chromosomal rearrangements, and suppression of recombination. The model species Arabidopsis thaliana and Brassica rapa are close relatives of papaya. All three species belong to the order Brassicales and their respective families, Caricaceae and Brassicaceae, diverged from a common ancestor 72 million years ago (Wikstrom et al., 2001). Since Arabidopsis and papaya have diverged, Arabidopsis has undergone two whole genome duplications (Blanc, 2003). This close relationship makes papaya an ideal out-group for comparative genomic studies. Not only does papaya of interest for genomic studies, but it is also an agriculturally significant crop and is one of the world’s most nutritious fruit per serving.

Allele-resolved single-cell multi-omics uncovers the dynamics and transcriptional kinetics of X-chromosome upregulation

Abstract: X-chromosome inactivation (XCI) and upregulation (XCU) are the major opposing chromosome-wide modes of gene regulation that collectively achieve dosage compensation in mammals, but the regulatory link between the two remains elusive. Here, we use allele-resolved single-cell RNA-seq combined with chromatin accessibility profiling to finely dissect the separate effects of XCI and XCU on RNA levels during mouse development. We uncover that balanced X dosage is flexibly attained through expression tuning by XCU in a sex- and lineage-specific manner along varying degrees of XCI and across developmental and cellular states. Male blastomeres achieve XCU upon zygotic genome activation while females experience two distinct waves of XCU, upon imprinted- and random XCI, and ablation of Xist impedes female XCU. Contrary to widely established models of mammalian dosage compensation, naive female embryonic cells carrying two active X chromosomes do not exhibit upregulation but express both alleles at basal level, yet collectively exceeding the RNA output of a single hyperactive allele. We show, in vivo and in vitro, that XCU is kinetically driven by X-specific modulation of transcriptional burst frequency, coinciding with increased compartmentalization of the hyperactive allele. Altogether, our data provide unprecedented insights into the dynamics of mammalian XCU, prompting a revised model of the chain in events of allelic regulation by XCU and XCI in unitedly achieving stable cellular levels of X-chromosome transcripts.

Genomic Imprinting and X Chromosome Dosage Compensation in Domestic Ruminants

Abstract: In diploid cells, genes are presumed to be expressed from both alleles to maintain gene dosage for normal development. However, a small number of genes reach haplosufficiency even with only one functional allele per cell. Most of these genes are regulated through genomic imprinting and X chromosome inactivation (XCI). DNA methylation is an essential epigenetic regulation for developmental programming in embryogenesis and play crucial roles in genomic imprinting and XCI. This dissertation presents 1) effects of maternal diets on genome imprinting in fetal sheep (Chapter Two), 2) dosage compensation of the X chromosomes in bovine germline, embryos and somatic tissues (Chapter Three), 3) Whole genome DNA methylation in bovine in vivo preimplantation development (Chapter Four). In chapter two, we report the first throughput study of genomic imprinting in sheep and report the identification of 13 new imprinted genes as well as demonstrating that maternal diets affect expression of imprinted genes in fetuses. Our results determine maternal diets influence imprinted gene expression while the parental-of-origin expression pattern was not affected, further suggesting that gene expression levels and imprinted patterns may be regulated through different epigenetic mechanisms. In chapter three, we reported the up-regulation of X chromosome in bovine germline, embryos and somatic tissues, supporting a balanced expression between a single active X and autosome pairs. However, deviating from Ohno’s theory, dosage compensation to rescue X haploinsufficiency appears to be an incomplete process for expressed genes but a complete process for “dosage-sensitive” genes. In chapter four, we adopted the scWGBS-seq method to comprehensive profile 5-MeC in single-cytosine Jingyue (Ellie) Duan – University of Connecticut, 2018 resolution in bovine sperm, immature oocyte, in vivo/vitro mature single oocyte, and in vivo developed 2-, 4-, 8-, 16-cell single embryos. We observed global demethylation during bovine embryo cleavage up to 8-cell stage and de novo methylation at 16-cell stage. Our results refined the current knowledge on bovine embryo DNA methylation dynamics and provide valuable resources for future studies.

Recent progress and open questions in Drosophila dosage compensation.

Abstract: Sexual dimorphism is observed in many traits across diverse taxa, and often it is quite extreme. Within a species, individuals of opposing sex can appear strikingly different, reflecting differences at the molecular level that may be similarly striking. Among the most extreme cases of such molecular sexual dimorphism is the quantity of sex chromosomes that each sex possesses. Hemizygous sex chromosomes are common to many species, and various mechanisms have evolved to regulate transcriptional activity to ensure appropriate sex chromosome-to-autosome gene expression stoichiometry. Among the most thoroughly investigated of these mechanisms is Drosophila melanogaster's male-specific lethal (MSL) complex-mediated dosage compensation. In Drosophila, the male X chromosome transcription is upregulated approximately two-fold in somatic tissues to counterbalance the effects of sex chromosome hemizygosity on transcript abundance. Despite dramatic advances in our understanding of the Drosophila dosage compensation, ...