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 and gene expression on the mammalian X chromosome: one plus one does not always equal two

Abstract: Counting chromosomes is not just simple math Although normal males and females differ in sex chromosome content (XY vs XX), X chromosome imbalance is tolerated because dosage compensation mechanisms have evolved to ensure functional equivalence In mammals this is accomplished by two processes—X chromosome inactivation that silences most genes on one X chromosome in females, leading to functional X monosomy for most genes in both sexes, and X chromosome upregulation that results in increased gene expression on the single active X in males and females, equalizing dosage relative to autosomes This review focuses on genes on the X chromosome, and how gene content, organization and expression levels can be influenced by these two processes Special attention is given to genes that are not X inactivated, and are not necessarily fully dosage compensated These genes that “escape” X inactivation are of medical importance as they explain phenotypes in individuals with sex chromosome aneuploidies and may impact normal traits and disorders that differ between men and women Moreover, escape genes give insight into how X chromosome inactivation is spread and maintained on the X

Systematic Analysis of the Determinants of Gene Expression Noise in Embryonic Stem Cells

Abstract: Isogenic cells in a common environment show substantial cell-to-cell variation in gene expression, often referred to as "expression noise." Here, we use multiple single-cell RNA-sequencing datasets to identify features associated with high or low expression noise in mouse embryonic stem cells. These include the core promoter architecture of a gene, with CpG island promoters and a TATA box associated with low and high noise, respectively. High noise is also associated with "conflicting" chromatin states-the absence of transcription-associated histone modifications or the presence of repressive ones in active genes. Genes regulated by pluripotency factors through super-enhancers show high and correlated expression variability, consistent with fluctuations in the pluripotent state. Together, our results provide an integrated view of how core promoters, chromatin, regulation, and pluripotency fluctuations contribute to the variability of gene expression across individual stem cells.

X chromosome-specific cDNA arrays: identification of genes that escape from X-inactivation and other applications

Abstract: Mutant alleles are frequently characterized by low expression levels. Therefore, cDNA array-based gene expression profiling may be a promising strategy for identifying gene defects underlying monogenic disorders. To study the potential of this approach, we have generated an X chromosome-specific microarray carrying 2423 cloned cDNA fragments, which represent up to 1317 different X-chromosomal genes. As a prelude to testing cell lines from patients with X-linked disorders, this array was used as a hybridization probe to compare gene expression profiles in lymphoblastoid cell lines from normal males, females and individuals with supernumerary X chromosomes. Measurable hybridization signals were obtained for more than half of the genes represented on the chip. A total of 53 genes showed elevated expression levels in cells with multiple X chromosomes and many of these were found to escape X-inactivation. Moreover, the detection of a male-viable deletion encompassing three genes illustrates the utility of this array for the identification of small unbalanced chromosome rearrangements.