Gene Expression

Association and spreading of the Drosophila dosage compensation complex from a discrete roX1 chromatin entry site Kageyama, Y. et al. EMBO J. 290, 2236–2245 (2001) [PubMed]

Last month's Highlights discussed mechanisms that underlie the spreading of repressive chromatin. This paper reports the spreading of active chromatin, which is required for dosage compensation in flies to increase X-linked transcription in males. Dosage compensation is controlled by the male-lethal specific (MLS) complex, comprising five proteins and two non-coding (roX) RNAs. MLS binds to chromatin entry sites, one of which is the roX1 gene. This study identifies a small DNase hypersensitive roX1 fragment that, when located on autosomes, produces an ectopic chromatin entry site, which binds the MSL complex, allowing it to spread into neighbouring regions. This occurs even when roX1 transcription is prevented, raising questions as to the role of the roX1 transcript.

Bacterial genetics

Regulation of differentiation to the infective stage of the protozoan parasite Leishmania major by tetrahydrobiopterin. Cunningham, M. L. et al. Science 292, 285–287 (2001)[PubMed]

Leishmania is an important human parasite, the life cycle of which involves an infective stage (in the sand-fly vector) and an uninfective stage (in vertebrate macrophages). Cunningham et al. investigate the mechanisms that underlie the progression from the uninfective to the infective stage, and discover that knocking out a gene involved in pteridine metabolism, PTR1, results in increased virulence. In normal development, PTR1 downregulation is necessary for the infective stage. This study reveals that virulence correlates inversely with PTR1 levels and that they can be used by Leishmania as a natural virulence-control mechanism to avoid killing its host.

Immunogenetics

Artemis, a novel DNA double-strand break repair/V(D)J protein, is mutated in severe combined immune deficiency. Moshous, D. et al. Cell 105, 177–186 (2001)[PubMed]

Human severe combined immunodeficiency with increased radiosensitivity (RS-SCID) is characterized by a defect, in V(D)J recombination, which causes RAG-induced double-stranded breaks to remain unrepaired, thus resulting in arrested B- and T-cell maturation. This study reports the positional cloning of Artemis, the RS-SCID disease gene, and the finding of eight independent mutations in RS-SCID patients, three of which involve deletions that span several exons. Artemis encodes a novel V(D)J recombination/DNA repair factor that belongs to the metallo-β-lactamase superfamily, but its precise role in DNA repair remains to be found.