Cruciform DNA, a non-double helix form of DNA, can be generated as an intermediate in genetic recombination as well as from palindromic sequences under the effect of supercoiling. Eukaryotic cells are equipped with a DNA-binding protein that selectively recognizes cruciform DNA. Biochemical and immunological data showed that this protein is HMG1, an evolutionarily conserved, essential, and abundant component of the nucleus. The interaction with a ubiquitous protein points to a critical role for cruciform DNA conformations.

The High Mobility Group Box (HMGB) chromosomal proteins have been known and studied for a long time, but we have only recently started to understand their biological functions. They now have a clear reputation for being important architectural factors: they facilitate the assembly of site‐specific DNA binding proteins to their cognate binding sites within chromatin. Beyond this intranuclear function, they also have an extracellular function, which will be the prime focus of this short review. ### The HMGB family: structure, expression and nuclear function The HMGB family comprises the three proteins HMGB1 (previously HMG1), HMGB2 (previously HMG2) and HMGB3 (previously HMG4 or HMG2b) (Bustin, 2001). The structure of these three proteins is highly conserved (>80% amino acid identity), and their biochemical properties are so far indistinguishable. HMGBs are composed of three different domains. The two homologous DNA binding domains, HMG boxes A and B, are each ∼75 amino acids in length. The C‐terminal domain is highly negatively charged, consisting of a continuous stretch of glutamate or aspartate residues, and is longest in HMGB1 and shortest in HMGB3 (reviewed in Bustin, 1999; Bianchi and Beltrame, 2000). HMGB1 is ubiquitous and only 10 times less abundant than core histones, at ∼106 molecules per typical mammalian cell. Expression of the other two family members is more restricted: HMGB3 is only expressed to a significant amount during embryogenesis (Vaccari et al ., 1998); HMGB2 is widely expressed during embryonic development, but restricted mainly to lymphoid organs and testis in the adult mouse (Ronfani et al ., 2001). The localization of these proteins in most cells is nuclear. In their nuclear identity, HMGB1 and HMGB2 bind to the minor groove of DNA, causing a local distortion of the double helix. They have little or no sequence preference, and they are recruited to the site of action by specific DNA binding proteins. HMGB1 has …

Mutations in SOX18 cause the human hypotrichosis-lymphedema-telangiectasia (HLT) syndrome. Their murine counterparts are the spontaneous ragged mutants, showing combined defects in hair follicle, blood vessel, and lymphatic vessel development. Mice null for Sox18 display only mild coat defects, suggesting a dominant-negative effect of Sox18/ragged mutations and functional redundancy between Sox18 and other Sox-F proteins. We addressed this point in zebrafish. The zebrafish homologs of Sox18 and of Sox7 are expressed in angioblasts and in the endothelial component of nascent blood vessels in embryos. Knockdown of either gene, using moderate doses of specific morpholinos, had minimal effects on vessels. In contrast, simultaneous knockdown of both genes resulted in multiple fusions between the major axial vessels. With combined use of transgenic lines and molecular markers, we could show that endothelial cells are specified, but fail to acquire a correct arteriovenous identity. Venous endothelial cell differentiation was more severely affected than arterial. Thus, sox7 and sox18 play redundant but collectively essential roles in the establishment of proper arteriovenous identity in zebrafish. Our data suggest that a defect in arteriovenous identity could be responsible for the formation of telangiectases in patients with HLT.

An optogenetic tool to silence neurons: Potassium channels in the cell membrane open and close in response to molecular signals to alter the local membrane potential. Cosentino et al. linked a light-responsive module to the pore of a potassium channel to build a genetically encoded channel called BLINK1 that is closed in the dark and opens in response to low doses of blue light. Zebrafish embryos expressing BLINK1 in their neurons changed their behavior in response to blue light. Science , this issue p. 707