Packaging of eukaryotic genomes into chromatin affects every process that occurs on DNA. The positioning of nucleosomes on underlying DNA plays a key role in regulation of these processes, as the nucleosome occludes underlying DNA sequences. Here, we review the literature on mapping nucleosome positions in various organisms, and discuss how nucleosome positions are established, what effect nucleosome positioning has on control of gene expression, and touch on the correlations between chromatin packaging, sequence evolution, and the evolution of gene expression programs.
Site-specific DNA recombination is important for basic cellular functions including viral integration, control of gene expression, production of genetic diversity and segregation of newly replicated chromosomes, and is used by bacteriophage λ to integrate or excise its genome into and out of the host chromosome. λ recombination is carried out by the bacteriophage-encoded integrase protein (λ -int) together with accessory DNA sites and associated bending proteins that allow regulation in response to cell physiology. Here we report the crystal structures of λ -int in higher-order complexes with substrates and regulatory DNAs representing different intermediates along the reaction pathway. The structures show how the simultaneous binding of two separate domains of λ -int to DNA facilitates synapsis and can specify the order of DNA strand cleavage and exchange. An intertwined layer of amino-terminal domains bound to accessory (arm) DNAs shapes the recombination complex in a way that suggests how arm binding shifts the reaction equilibrium in favour of recombinant products.λ -int catalyses an ordered, pair-wise exchange of four DNA strands between two different pairs of recombination substrates 1,2 . During integration, λ -int aligns the bacteriophage attachment site attP with the bacterial attachment site attB and recombines these sequences to generate the recombination joints attL and attR flanking the integrated prophage (Fig. 1a, b). During the transition to lytic growth, the bacteriophage DNA is excised to regenerate attP and attB. In both reactions, the analogous pair of DNA strands ('top' strands) is exchanged first 3,4 to form a branched, four-way DNA intermediate known as a Holliday junction. Subsequent exchange of 'bottom' strands resolves the Holliday junction into linear recombinant products 2 . Although integration and excision might appear to be reciprocal reactions ( Fig. 1), they involve different substrates and are effectively irreversible 5 . The recombination machinery is configured differently during integration or excision by two different overlapping subsets of accessory factors and binding sites that bend the DNA arms flanking the core sites of strand exchange 2,6 . DNA bending is a prerequisite for the simultaneous interactions with arm and core sites 6-9 that deliver λ -int to lower-affinity core sites 10 . Arm-binding interactions allosterically enhance the fidelity of DNA strand exchange 11 and bias the outcome of Holliday junction resolution in favour of the recombined products 12 .Correspondence and requests for materials should be addressed to T.E. (tome@hms.harvard.edu).. * These authors contributed equally to this work.Supplementary Information is linked to the online version of the paper at www.nature.com/nature. These structures suggest that only a small shift in subunit packing is sufficient to redirect DNA cleavage and exchange activities from one pair of strands to the other, in order to resolve the Holliday junction into products 13,14 . However, the molecular mechanism o...
The histone variant H2A.Z plays key roles in gene expression, DNA repair, and centromere function. H2A.Z deposition is controlled by SWR-C chromatin remodeling enzymes that catalyze the nucleosomal exchange of canonical H2A with H2A.Z. Here we report that acetylation of histone H3 on lysine 56 (H3-K56Ac) alters the substrate specificity of SWR-C, leading to promiscuous dimer exchange in which either H2A.Z or H2A can be exchanged from nucleosomes. This result was confirmed in vivo, where genome-wide analysis demonstrated widespread decreases in H2A.Z levels in yeast mutants with hyperacetylated H3K56. Our work also suggests that a conserved SWR-C subunit may function as a “lock” that prevents removal of H2A.Z from nucleosomes. Our study identifies a histone modification that regulates a chromatin remodeling reaction and provides insights into how histone variants and nucleosome turnover can be controlled by chromatin regulators.
Tracking of ancestral histone proteins over multiple generations of genome replication in yeast reveals that old histones move along genes from 3′ toward 5′ over time, and that maternal histones move up to around 400 bp during genomic replication.
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