ABSTRACT
In 2001 it was established that, contrary to our previous understanding, a mechanism exists that equalises the expression levels of Z chromosome genes found in male (ZZ) and female (ZW) birds (McQueen et al. 2001). More recent large scale studies have revealed that avian dosage compensation is not a chromosome-wide phenomenon and that the degree of dosage compensation can vary between genes (Itoh et al. 2007; Ellegren et al. 2007). Although, surprisingly, dosage compensation has recently been described as absent in birds (Mank and Ellegren 2009b), this interpretation is not supported by the accumulated evidence, which indicates that a significant proportion of Z chromosome genes show robust dosage compensation and that a particular cluster of such dosage compensated genes can be found on the short arm of the Z chromosome. The implications of this new picture of avian dosage compensation for avian sex determination are discussed, along with a possible mechanism of avian dosage compensation.
Subject(s)
Birds/genetics , Dosage Compensation, Genetic , Sex Chromosomes , Animals , Female , Male , Reverse Transcriptase Polymerase Chain Reaction , Sex Determination Processes , Transcription Factors/geneticsABSTRACT
Birds undergo genetic sex determination using a ZW sex chromosome system. Although the avian mechanisms of neither sex determination nor dosage compensation are understood, a female-specific non-coding RNA (MHM) is expressed soon after fertilisation from the single Z chicken chromosome and is likely to have a role in one or both processes. We have now discovered a prominent female-specific modification to the Z chromatin in the region of the MHM locus. We find that chicken chromatin at Zp21, including the MHM locus, is strongly enriched for acetylation of histone H4 at lysine residue 16 in female but not male chromosomes. Interestingly, this specific histone modification is also enriched along the length of the up-regulated Drosophila melanogaster male X chromosome where it plays a vital role in the dosage compensation process.
Subject(s)
Chickens/genetics , Chromatin/metabolism , Histones/metabolism , Sex Chromosomes/genetics , Acetylation , Animals , Cells, Cultured , Dosage Compensation, Genetic , Female , Fibroblasts , In Situ Hybridization, Fluorescence , Male , Sex FactorsABSTRACT
The genes MBD1 and MBD2 encode methyl-CpG binding proteins that suppress transcription from methylated promoters. In contrast, CGBP encodes a protein that binds promoters containing unmethylated CpG and stimulates transcription. All three are located on human chromosome 18q21, a region of frequent loss of heterozygosity in several cancers. These genes therefore represent candidate tumour suppressor genes, whose loss of function could affect the normal regulation of gene expression, whether by lack of complete suppression of genes normally silenced (via loss of MBD1 and MBD2) or by some loss of activation of genes normally expressed (via loss of CGBP), either way contributing to the tumorigenic phenotype. We have confirmed by fluorescent in situ hybridization that MBD1 and MBD2 bracket the DCC locus giving a gene order of MBD1/CGBP-DCC 5'-DCC 3'-MBD2. Mutation analyses by single-stranded conformation polymorphism in colon and lung cancer cell lines and primary tumours revealed a small number of mutations, suggesting only a limited role of these genes in human tumorigenesis.