Gene Regulation

Identifying regulatory networks by combinatorial analysis of promoter elements. Pilpel, Y. et al. Nature Genet. 29, 153–159 (2001) [PubMed]

The use of microarray technology for transcriptional profiling and cluster analysis is a powerful approach for finding coregulated genes and the promoter motifs that control transcription. Pilpel et al. have extended this approach by studying the combinatorial action of regulatory motifs in Saccharomyces cerevisiae. They identified pairs of motifs that act in a synergistic manner to provide tighter transcriptional regulation than either motif alone. The resulting network of interactions shows how a relatively small number of transcription factors might act in concert to regulate gene expression under a broad range of growth conditions.

Development

A murine model of the Holt–Oram syndrome defines roles of the T-box transcription factor Tbx5 in cardiogenesis and disease. Bruneau, B. G. et al. Cell 109, 709–721 (2001) [PubMed]

Several T-box (Tbx) gene family members are involved in dominant congenital heart disorders — TBX5 in Holt–Oram syndrome (HOS) and probably TBX1 in DiGeorge syndrome (see Elizabeth Lindsay's review, p858). This Tbx5-knockout study provides new insight into how Tbx5 haploinsufficiency causes HOS-like heart defects in mice. Tbx+/− mice show the reduced expression of many genes, most markedly that of atrial natriuretic factor (Anf) and connexin 40 (Cx40). The authors discovered that Anf and Cx40 are activated when Tbx5 and Nkx2-5 interact at their promoters, indicating a mechanism for the haploinsufficient effects of Tbx5. Misregulation of Cx40 could underlie the heart-conduction defects in Tbx5+/− mice and HOS patients. Their findings also shed light on the condition's variability and on cardiac malformations caused by other transcription factor mutations.

Transposable elements

Mobilization of a Drosophila transposon in the Caenorhabditis elegans germ line. Bessereau, J.-L. et al. Nature 413, 70–74 (2001) [PubMed]

Although C. elegans has several native transposon types, they cannot be used to manipulate the worm genome because they are too numerous to serve as unique gene tags and because different transposon types can be activated at the same time, making them difficult to trace. This paper shows the successful mobilization of a foreign element — the Drosophila mariner element, Mos1 — in the worm. Mos1 has the essential qualities of a regulable transposon: it can be mobilized in the soma and germ line — where its insertion point can be identified by PCR — and it can be mutagenic by imperfect excision.