Dosage compensation

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

PionX sites mark the X chromosome for dosage compensation

Abstract: Recognition of the X chromosome by the dosage compensation complex in Drosophila relies on the sequence and shape of PionX sites. In male Drosophila, the male-specific lethal dosage compensation complex (MSL-DCC) discriminates the X chromosome from autosomes and doubles the transcription output of the X chromosome selectively. Some sequence elements are known to be involved in targeting the DCC to the X chromosome, but it has not been clear how X-chromosomal sequence elements are selected from the thousands of similar sequences in the genome. Here, Peter Becker and colleagues show that recognition of the X chromosome is an intrinsic feature of the MSL-DCC. The MSL2 subunit uses two distinct DNA interaction surfaces to distinguish a subset of MSL2 binding sites — termed PionX — which are defined not only by additional sequence features but also by a distinct DNA conformation (base roll). These sites originated early during X chromosome evolution. The results are an example of how transcription factors can distinguish a minority of functional DNA elements from a large pool of similar but non-functional sequences. The rules defining which small fraction of related DNA sequences can be selectively bound by a transcription factor are poorly understood. One of the most challenging tasks in DNA recognition is posed by dosage compensation systems that require the distinction between sex chromosomes and autosomes. In Drosophila melanogaster, the male-specific lethal dosage compensation complex (MSL-DCC) doubles the level of transcription from the single male X chromosome, but the nature of this selectivity is not known1. Previous efforts to identify X-chromosome-specific target sequences were unsuccessful as the identified MSL recognition elements lacked discriminative power2,3. Therefore, additional determinants such as co-factors, chromatin features, RNA and chromosome conformation have been proposed to refine targeting further4. Here, using an in vitro genome-wide DNA binding assay, we show that recognition of the X chromosome is an intrinsic feature of the MSL-DCC. MSL2, the male-specific organizer of the complex, uses two distinct DNA interaction surfaces—the CXC and proline/basic-residue-rich domains—to identify complex DNA elements on the X chromosome. Specificity is provided by the CXC domain, which binds a novel motif defined by DNA sequence and shape. This motif characterizes a subclass of MSL2-binding sites, which we name PionX (pioneering sites on the X) as they appeared early during the recent evolution of an X chromosome in D. miranda and are the first chromosomal sites to be bound during de novo MSL-DCC assembly. Our data provide the first, to our knowledge, documented molecular mechanism through which the dosage compensation machinery distinguishes the X chromosome from an autosome. They highlight fundamental principles in the recognition of complex DNA elements by protein that will have a strong impact on many aspects of chromosome biology.

Characterization of BEAF Mutations Isolated by Homologous Recombination in Drosophila

Abstract: The Drosophila BEAF-32A and BEAF-32B proteins bind to the scs′ insulator and to hundreds of other sites on Drosophila chromosomes. These two proteins are encoded by the same gene. We used ends-in homologous recombination to generate the null BEAFAB-KO allele and also isolated the BEAFA-KO allele that eliminates production of only the BEAF-32A protein. We find that the BEAF proteins together are essential, but BEAF-32B alone is sufficient to obtain viable flies. Our results show that BEAF is important for both oogenesis and development. Maternal or zygotic BEAF is sufficient to obtain adults, although having only maternal BEAF impairs female fertility. In the absence of all BEAF, a few fertile but sickly males are obtained. Using both a chromosomal position-effect assay and an enhancer-blocking assay, we find that BEAF is necessary for scs′ insulator function. Lack of BEAF causes a disruption of male X polytene chromosome morphology. However, we did not find evidence that dosage compensation was affected. Position-effect variegation of the wm4h allele and different variegating y transgenes was enhanced by the knockout mutation. Combined with the effects on male X polytene chromosomes, we conclude that BEAF function affects chromatin structure or dynamics.

Nonrandom representation of sex-biased genes on chicken Z chromosome.

Abstract: Several lines of evidence suggest that the X chromosome of various animal species has an unusual complement of genes with sex-biased or sex-specific expression. However, the study of the X chromosome gene content in different organisms provided conflicting results. The most striking contrast concerns the male-biased genes, which were reported to be almost depleted from the X chromosome in Drosophila but overrepresented on the X chromosome in mammals. To elucidate the reason for these discrepancies, we analysed the gene content of the Z chromosome in chicken. Our analysis of the publicly available expressed sequence tags (EST) data and genome draft sequence revealed a significant underrepresentation of ovary-specific genes on the chicken Z chromosome. For the brain-expressed genes, we found a significant enrichment of male-biased genes but an indication of underrepresentation of female-biased genes on the Z chromosome. This is the first report on the nonrandom gene content in a homogametic sex chromosome of a species with heterogametic female individuals. Further comparison of gene contents of the independently evolved X and Z sex chromosomes may offer new insight into the evolutionary processes leading to the nonrandom genomic distribution of sex-biased and sex-specific genes.