Dosage compensation

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

The Drosophila roX1 RNA gene can overcome silent chromatin by recruiting the male-specific lethal dosage compensation complex.

Abstract: The Drosophila MSL complex consists of at least six proteins and two noncoding roX RNAs that mediate dosage compensation. It acts to remodel the male9s X chromatin by covalently modifying the amino terminal tails of histones. The roX1 and roX2 genes are thought to be nucleation sites for assembly and spreading of MSL complexes into surrounding chromatin where they roughly double the rates of transcription. We generated many transgenic stocks in which the roX1 gene was moved from its normal location on the X to new autosomal sites. Approximately 10% of such lines displayed unusual sexually dimorphic expression patterns of the transgene9s mini- white eye-color marker. Males often displayed striking mosaic pigmentation patterns similar to those seen in position-effect variegation and yet most inserts were in euchromatic locations. In many of these stocks, female mini- white expression was very low or absent. The male-specific activation of mini- white depended upon the MSL complex. We propose that these transgenes are inserted in several different types of repressive chromatin environments that inhibit mini- white expression. Males are able to overcome this silencing through the action of the MSL complex spreading from the roX1 gene and remodeling the local chromatin to allow transcription. The potency with which an ectopic MSL complex overcomes silent chromatin suggests that its normal action on the X must be under strict regulation.

The sisterless-b function of the Drosophila gene scute is restricted to the stage when the X:A ratio determines the activity of Sex-lethal.

Abstract: The gene scute (sc) has a dual function: the scute function which is involved in neurogenesis and the sisterless-b function which is involved in generating the X:A signal that determines the state of activity of Sxl, a gene that controls sex determination and dosage compensation. We show here that the lethal phase of sc- females is embryonic and caused by the lack of Sxl function. We also analyze the time in development when sc and Sxl interact by means of (a) determining the thermosensitive phase (TSP) of the interaction between Sxl and sc and (b) a chimeric gene in which sc is under the control of a heat-shock promoter (HSSC-3). Pulses of sc expression from the HSSC-3 activate Sxl only at a very specific and early stage in development, which coincides with the TSP of the interaction between sc and Sxl. It corresponds to the syncytial blastoderm stage and coincides with the time when the X:A signal regulates Sxl. At this stage sc undergoes a homogeneous transient expression in wild-type flies. We conclude that the sc expression at the syncytial blastoderm is responsible for its sisterless-b function. Since sc expression from the HSSC-3 fully suppresses the sisterless-b phenotype, we further conclude that the sisterless-b function is exclusively provided by the sc protein. Finally, we have analyzed, by in situ hybridization, the effect of sc and sis-a mutations on the embryonic transcription of Sxl. Our results support the view that the control of Sxl by the X:A signal occurs at the transcriptional level.

Effects of the maleless mutation on X and autosomal gene expression in Drosophila melanogaster.

Abstract: The mutational effect of the maleless (mle) gene in Drosophila has been reexamined. Earlier work had suggested that mle along with other male-lethal genes was responsible for hypertranscription of the X chromosome in males to bring about dosage compensation. Prompted by studies on dosage sensitive regulatory genes, we tested for effects of mlets on the phenotypes of 16 X or autosomal mutations in adult escapers of lethality. In third instar larvae, prior to the major lethal phase of mle, we examined activities of 6 X or autosomally encoded enzymes, steady state mRNA levels of 15 X-linked or autosomal genes and transcripts from two large genomic segments derived from either the X or from chromosome 2 and present in yeast artificial chromosomes. In contrast to the previously hypothesized role, we detected pronounced effects of mle on the expression of both X-linked and autosomal loci such that a large proportion of the tested genes were increased in expression, while only two X-linked loci were reduced. The most prevalent consequence was an increase of autosomal gene expression, which can explain previously observed reduced X:autosome transcription ratios. These observations suggest that if mle plays a role in the discrimination of the X and the autosomes, it may do so by modification of the effects of dosage sensitive regulatory genes.

Mapping of the distal boundary of the X-inactivation center in a rearranged X chromosome from a female expressing XIST

Abstract: A female patient with primary amenorrhea, immature secondary sexual characteristics, and tall stature was found to have a normal X chromosome and a rearranged X [rea(X)] chromosome that resembled an 'isochromosome' Xp, but retained the proximal portion of Xq. The rea(X) was interpreted as rec(X)dup p,inv(X)(p11.4q13). Replication studies demonstrated that the rea(X) was always the late-replicating and, therefore, presumably inactive X chromosome, which must contain the X-inactivation center. Consistent with this interpretation, fluorescence in situ hybridization demonstrated that the rea(X) retained the XIST gene, and reverse transcription polymerase chain reaction analysis showed that XIST was expressed in the patient's cells. By fluorescence in situ hybridization with previously mapped probes, the breakpoint of the rea(X) was located within an approximately 500-kb region located approximately 200 to 700 kb distal to the XIST locus. This is the closest breakpoint distal to XIST in an inactivated X chromosome and, therefore, defines a new distal boundary for the X-inactivation center in humans.