Evolution of nucleosome occupancy: conservation of global properties and divergence of gene-specific patterns

To examine the role of nucleosome occupancy in the evolution of gene expression, we measured the genome-wide nucleosome profiles of four yeast species, three belonging to the Saccharomyces sensu stricto lineage and the more distantly related Candida glabrata. Nucleosomes and associated promoter elements at C. glabrata genes are typically shifted upstream by ～20 bp, compared to their orthologs from sensu stricto species. Nonetheless, all species display the same global organization features first described for Saccharomyces cerevisiae: a stereotypical nucleosome organization along genes and a division of promoters into those that contain or lack a pronounced nucleosome-depleted region (NDR), with the latter displaying a more dynamic pattern of gene expression. Despite this global similarity, however, nucleosome occupancy at specific genes diverged extensively between sensu stricto and C. glabrata orthologs (～50 million years). Orthologs with dynamic expression patterns tend to maintain their lack of NDR, but apart from that, sensu stricto and C. glabrata orthologs are nearly as similar in nucleosome occupancy patterns as nonorthologous genes. This extensive divergence in nucleosome occupancy contrasts with a conserved pattern of gene expression. Thus, while some evolutionary changes in nucleosome occupancy contribute to gene expression divergence, nucleosome occupancy often diverges extensively with apparently little impact on gene expression.     

两种模式生物核小体定位比较研究

在对两种模式生物酵母与果蝇胚胎期核小体定位进行研究时,发现不同物种间以及同一物种中不同表达模式基因上的核小体分布呈现出差显著异性。在总体上,转录起始位点附近的酵母核小体NFR区域比果蝇的NFR短。经基因中心对齐后,酵母与果蝇胚胎期沉默型基因的核小体缺失区域的两个边界中间处共同呈现了一个明确有着均匀间隔的核小体数n,且随着基因长度L的变长其周期性特性逐渐变模糊,但果蝇的图谱表现的更为复杂。结果表明,从单细胞酵母生物到多细胞果蝇生物间基因组的进化过程中,核小体组织的演化既有变异性,也具有保守性。     

Functionally distinct nucleosome-free regions in yeast require Rad7 and Rad16 for nucleotide excision repair

In yeast, Rad7 and Rad16 are two proteins required for nucleotide excision repair (NER) of non-transcribed chromatin. They have roles in damage recognition, in the postincision steps of NER, and in ultraviolet-light-dependent histone H3 acetylation. Moreover, Rad16 is an ATP-ase of the SNF2 superfamily and therefore might facilitate chromatin repair by nucleosome remodelling. Here, we used yeast rad7 Delta rad16 Delta mutants and show that Rad7-Rad16 is also required for NER of UV-lesions in three functionally distinct nucleosome-free regions (NFRs), the promoter and 3'-end of the URA3 gene and the ARS1 origin of replication. Moreover, rapid repair of UV-lesions by photolyase confirmed that nucleosomes were absent and that neither UV-damage formation nor rad7 Delta rad16 Delta mutations altered chromatin accessibility in NFRs. The data are consistent with a role of Rad7-Rad16 in damage recognition and processing in absence of nucleosomes. An additional role in nucleosome remodelling is discussed.     

The sheep genome contributes to localization of control elements in a human gene with complex regulatory mechanisms

Genes that show complex tissue-specific and temporal control by regulatory elements located outside their promoters present a considerable challenge to identify the sequences involved. The rapid accumulation of genomic sequence information for a number of species has enabled a comparative phylogenetic approach to find important regulatory elements. For some genes, which show a similar pattern of expression in humans and rodents, genomic sequence information for these two species may be sufficient. Others, such as the cystic fibrosis transmembrane conductance regulator (CFTR) gene, show significant divergence in expression patterns between mouse and human, necessitating phylogenetic approaches involving additional species. The ovine CFTR gene has a temporal and spatial expression pattern that is very similar to that of human CFTR. Comparative genomic sequence analysis of ovine and human CFTR identified high levels of homology between the core elements in several potential regulatory elements defined as DNase I hypersensitive sites in human CFTR. These data provide a case for the power of an artiodactyl genome to contribute to the understanding of human genetic disease.