Dosage compensation

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

Battle of the sexes: Conflict over dosage-sensitive genes and the origin of X chromosome inactivation

Abstract: Males have been short-changed in the X chromosome department: they only get one copy of the chromosome and the genes that it carries, whereas females get two. Differences in gene dose often translate into differences in protein levels, potentially putting males at a disadvantage compared with their sisters. Female placental and marsupial mammals inactivate one of their two X chromosomes, effectively silencing gene expression from the inactive X and seemingly putting themselves at the same disadvantage as their brothers. In PNAS, Pessia et al. (1) show that female X chromosome inactivation (XCI) is not in fact an act of solidarity by females but rather a result of the evolutionary tug of war over gene expression and sex chromosome dosage compensation that occurs between the sexes on the X chromosome.

Sublocalisation of the X breakpoint in the translocation (X; 18)(p11.2; q11.2) primary change in synovial sarcomas.

Abstract: A specific translocation between chromosomes X and 18 was identified in synovial sarcomas. From a girl with synovial sarcoma, we isolated two clones with t(X; 18)(p11.2; q11.2) and which had lost the normal X chromosome. Southern blot analysis of DNA from the tumor, the patient and her parents demonstrated that the normal X chromosome, lost in the tumor, was the paternal one. A somatic hybrid cell line was established by fusing tumor cells (after passages on athymic mice) to an HPRT deficient hamster cell line. By cytogenetic, in situ hybridization and molecular analysis, it was found to contain the derivative (X) chromosome in the absence of the der (18) chromosome. To determine the position of the breakpoint on the X chromosome, Southern blots of DNA from this hybrid were hybridized to [32P]-labelled X chromosome probes. DXS146 and DXS255 were retained in the hybrid cell line whereas GAPDP1, the ARAF1 and TIMP proto-oncogenes were not present, indicating that the breakpoint lies proximal to GAPD1, ARAF1 and TIMP and distal to DXS255 and DXS146. Results obtained from other authors are compared. Further studies will be necessary to determine the extent of variation of the breakpoint in different tumors.

Severe phenotype resulting from an active ring X chromosome in a female with a complex karyotype: characterisation and replication study.

Abstract: We report on the characterisation of a complex chromosome rearrangement, 46,X,del(Xq)/47,X,del(Xq),+r(X), in a female newborn with multiple malformations. Cytogenetic and molecular methods showed that the del(Xq) contains the XIST locus and is non-randomly inactivated in all metaphases. The tiny r(X) chromosome gave a positive FISH signal with UBE1, ZXDA, and MSN cosmid probes, but not with a XIST cosmid probe. Moreover, it has an active status, as shown by a very short (three hour) terminal BrdU pulse followed by fluorescent anti-BrdU antibody staining. The normal X is of paternal origin and both rearranged chromosomes originate from the same maternal chromosome. We suggest that both abnormal chromosomes result from the three point breakage of a maternal isodicentric idic(X)(q21.1). Finally, the phenotype of our patient is compared to other published cases and, despite the absence of any 45,X clone, it appears very similar to those with a 45,X/46,X,r(X) karyotype where the tiny r(X) is active.

Abnormal X-Chromosome Dosage Compensation as a Possible Cause of Early Developmental Failure in Mice (X-chromosome inactivation/trophectoderm/imprinting/embryonic development)

Abstract: An extra maternally derived X chromosome (XM) but not a paternally derived one (XP) is detrimental in early mouse embryogenesis resulting in failure to form the ectoplacental cone and extra-embryonic ectoderm. Cytogenetic studies suggested that two XMchromosomes remain active in the trophectoderm and possibly also the primitive endoderm, in which XPis preferentially inactivated in normal female embyos. Two copies of an active X chromosome due to maternal imprinting seem to prevent further differentiation of the trophectoderm.

The Drosophila Y chromosome affects heterochromatin integrity genome-wide

Abstract: The Drosophila Y chromosome is gene poor and mainly consists of silenced, repetitive DNA. Nonetheless, the Y influences expression of hundreds of genes genome-wide, possibly by sequestering key components of the heterochromatin machinery away from other positions in the genome. To directly test the influence of the Y chromosome on the genome-wide chromatin landscape, we assayed the genomic distribution of histone modifications associated with gene activation (H3K4me3), or heterochromatin (H3K9me2 and H3K9me3) in fruit flies with varying sex chromosome complements (X0, XY and XYY males; XX and XXY females). Consistent with the general deficiency of active chromatin modifications on the Y, we find that Y gene dose has little influence on the genomic distribution of H3K4me3. In contrast, both the presence and the number of Y chromosomes strongly influence genome-wide enrichment patterns of repressive chromatin modifications. Highly repetitive regions such as the pericentromeres, the dot, and the Y chromosome (if present) are enriched for heterochromatic modifications in wildtype males and females, and even more strongly in X0 flies. In contrast, the additional Y chromosome in XYY males and XXY females diminishes the heterochromatic signal in these normally silenced, repeat-rich regions, which is accompanied by an increase in expression of Y-linked repeats. We find hundreds of genes that are expressed differentially between individuals with aberrant sex chromosome karyotypes, many of which also show sex-biased expression in wildtype Drosophila. Thus, Y chromosomes influence heterochromatin integrity genome-wide, and differences in the chromatin landscape of males and females may also contribute to sex-biased gene expression and sexual dimorphisms.