Mist1: a novel basic helix-loop-helix transcription factor exhibits a developmentally regulated expression pattern

An equilibrium between positive and negative regulation of immunoreceptor signaling leads to the proper execution of lymphocyte activation. Tyrosine phosphorylation is the initial event in antigen receptor-induced lymphocyte activation. It is generally accepted that protein tyrosine kinases are involved in positive regulation, whereas protein tyrosine phosphatases are important for the negative regulation of tyrosine phosphorylation-dependent processes. However, the interaction between protein tyrosine kinases and protein tyrosine phosphatases is complex. This article discusses the role of two protein tyrosine phosphatases. CD45 and SHP-1, in the regulation of immunoreceptor signaling. SHP-1 acts as a negative regulator for several immunoreceptors, including those for T- and B-cell antigen receptors. The major role of CD45 is in the positive regulation of T- and B-cell antigen receptor signaling.     

Math5 encodes a murine basic helix-loop-helix transcription factor expressed during early stages of retinal neurogenesis

We have identified Math5, a mouse basic helix-loop-helix (bHLH) gene that is closely related to Drosophila atonal and Xenopus Xath5 and is largely restricted to the developing eye. Math5 retinal expression precedes differentiation of the first neurons and persists within progenitor cells until after birth. To position Math5 in a hierarchy of retinal development, we compared Math5 and Hes1 expression in wild-type and Pax6-deficient (Sey) embryos. Math5 expression is downregulated in Sey/+ eyes and abolished in Sey/Sey eye rudiments, whereas the bHLH gene Hes1 is upregulated in a similar dose-dependent manner. These results link Pax6 to the process of retinal neurogenesis and provide the first molecular correlate for the dosage-sensitivity of the Pax6 phenotype. During retinogenesis, Math5 is expressed significantly before NeuroD, Ngn2 or Mash1. To test whether these bHLH genes influence the fates of distinct classes of retinal neurons, we ectopically expressed Math5 and Mash1 in Xenopus retinal progenitors. Unexpectedly, lipofection of either mouse gene into the frog retina caused an increase in differentiated bipolar cells. Directed expression of Math5, but not Xath5, in Xenopus blastomeres produced an expanded retinal phenotype. We propose that Math5 acts as a proneural gene, but has properties different from its most closely related vertebrate family member, Xath5.     

Negative regulation of transcription by anti-sigma factors

The identification, mapping and eventual cloning of genes which determine or influence important epidemiological traits in parasites can have great benefits for the control of parasitic disease. In this review, strategies are outlined for identifying genetic markers for complex, quantitative traits. A genetic marker is a variable DNA sequence which co-occurs with a variable quantitative trait. Candidate markers are chosen because they are thought to directly influence the trait whereas random markers are expected to be linked to another DNA sequence which influences the trait. Association studies compare the value of a quantitative trait between different marker genotype classes in a population, without regard to family structure. Linkage studies compare the value of a quantitative trait between marker genotype classes within families or within a population (usually derived from a cross between inbred lines) which is segregating for both marker and quantitative trait loci. The most commonly used analytical methods for determining the significance of association or linkage between marker and quantitative trait loci, and for estimating parameters such as recombination rate and quantitative gene action, are least-squares and maximum likelihood. Both methods may be used to test either single markers or the interval between flanking markers, and both suffer from the need to minimize type I and type II error rates with multiple tests.     

Structural and functional aspects of basic helix-loop-helix protein folding by heat-shock protein 90

The assembly and folding of nascent polypeptides are mediated in vivo by molecular chaperones, many of which are members of the heat-shock family of proteins. We have shown previously that heat-shock protein 90 (HSP90) folds an inactive fraction of a recombinant basic helix-loop-helix (bHLH) protein generated in Escherichia coli (MyoD) into its active conformation. We show here that HSP90 also folds another bHLH protein (E12) and heterodimers of E12/MyoD into their active conformations. By purifying inactive heterodimers of E12/MyoD and subsequently rendering them active in binding DNA by treatment with HSP90, we show that one folding step mediated by HSP90 occurs after oligomerization of the bHLH protein monomers. A series of deletion mutants is used to identify the 48-amino acid region of HSP90 that confers bHLH folding activity, which lies near the COOH terminus. This region is required for activation of DNA binding of MyoD and E12 homodimers and E12/MyoD heterodimers.