how do you make a kidney?

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Page 1: How do you make a kidney?

TRENDS in Genetics Vol.17 No.7 July 2001

http://tig.trends.com 0168–9525/01/$ – see front matter © 2001 Elsevier Science Ltd. All rights reserved.

381News&Comment

Reduced gene expressionduring memory consolidationIt has long been recognized that changes ingene expression occur when memories arebeing laid down. However, a study of globalgene expression changes during memoryconsolidation found that this processsurprisingly involves a widespread decrease,rather than increase, in gene expression.Dr Sebastiano Cavallaro and colleagues useda well-established behavioral technique,known as conditioning, to create long-termmemories in rabbits. Then, using high-density cDNA microarrays, they examinedthe changes in gene expression in the area of the brain associated with this type ofmemory. Although some genes showedincreased expression, the majority, includingmany novel expressed sequence tags (ESTs),showed a marked decrease. Cavallaro et al.propose that this decrease in gene expressioncould represent a relaxation of inhibitoryprocesses that prevent the formation ofunnecessary memories. [Cavallaro, S. et al.(2001) Eur. J. Neurosci. 13, 1809–1815] AI

Silent DNA speakingBy raising the temperature of yeast cellsmoderately, researchers at Louisiana StateUniversity Health Science Center havebroken through the heterochromatin barrierthat keeps many genes ‘silent’. Group leader David Gross said, ‘Until now, genessheathed in heterochromatin were assumedincapable of being expressed due to anabsence of trigger proteins. This researchshows that these proteins do naturallypenetrate heterochromatin, but once insidecannot function…heating the cells activatesthese proteins, causing a heat-responsivegene to be expressed at a very high rate.’Genes in the heated cells reached up to500 times their normal rate of expression.

The researchers found that even whenthe genes were not active, their promotersbound an activator (HSF) and twocomponents of the preinitiation complex,TBP and Pol II, as well as the expectedsilencing proteins (Sirs). This suggests that Sir silencing proteins regulate geneexpression not by restricting access to DNA, but by blocking a step downstream of the preinitiation complex recruitment.Interestingly, activation of silent promoterchromatin by heat shock did not displacehistones or change their acetylation state.[Sekinger, E.A. and Gross, D.S. (2001) Cell105, 403–414] PL

Genetic investigations intoIndia’s caste system

The higher castes in India are genetically morerelated to Europeans than to Asians. However,the lower castes are more Asian. The ~1 billionpopulation of India is divided into severalcastes, and intermingling between castes bymarriage is still largely restricted by society.An international team led by MichaelBamshad at the University of Utah analyzedpolymorphic markers on the paternallyinherited Y chromosome and the maternallyinherited mitochondrial DNA. Among highercastes, the markers on the Ychromosome weremore related to Europeans than to Asians.However, examination of the maternallyderived mitochondrial DNA showed that for allcastes, maternal origin was probably Asian.This finding supports the notion that men fromWest Eurasia entered India, mixed with thelocal Dravidic-speaking population andappointed themselves to higher ranks of anexisting caste system. Alternatively, these WestEurasians might have established the castesystem to legitimize their power. [Bamshad, M.et al. (2001) Genome Res. 11, 994–1004] AP

Antibiotic resistance genesback in the food chainGenes resistant to tetracycline have beenfound in groundwater as far as 250 mdownstream from two swine facilities that useantibiotics as growth promoters. The findingis significant because it shows the potentialfor spreading resistance back into the foodchain of animals and people, say researchersfrom the University of Illinois and Illinois StateGeological Survey. Using standard PCR, theyanalyzed samples from lagoons, wells andgroundwater on and near two Illinois facilities.The researchers could identify the trail takenby the resistance genes as the DNA in thesamples matched the resistance genespreviously identified in livestock and feed.[Chee-Sanford, J.C. et al. (2001) Appl. Env.Microbiol. 67, 1494–1592] PL

The makings of beautifulbuttocksThe genes that give rise to the callipyge(beautiful buttocks) phenotype in sheephave been identified and completelysequenced. Callipyge results in muscularhypertrophy in the hindquarters and is only manifest when the mutation (clpg) is inherited from the father. The study, ledby Michel Georges at the University ofLiege, Belgium, identified a total of sixtranscripts from the clpg locus, four ofwhich were novel. As predicted, all thegenes identified are subject to genomicimprinting (silencing of expressiondependent on which the parent the alelleoriginated from), and all show pronouncedexpression in skeletal muscle. What isstriking is that of the six transcripts, fourmight not encode proteins. These fourcould encode ‘effector RNAs’; anincreasingly common discovery atimprinted domains. [Charlier, C. et al.(2001) Genome Res. 11, 850–862] AI

How do you make a kidney? The step-by-step development of amammalian kidney, from its earlybeginnings in the embryo to its adult role as a vital organ, has now been defined at the level of gene expression.Sanjay Nigam and his group at theUniversity of California School ofMedicine, San Diego, CA, studied ratkidneys using DNA microarrays.According to Nigam, ‘Roughly a third of all chronic kidney disease in children is related to a disorder of kidneydevelopment. This study is hopefully thefirst of a series in which we aim to identifyspecific subsets of genes necessary fordifferent processes which, together, leadto formation of the kidney.’

In the early stages of development,many genes involved in DNA, RNA andprotein production were upregulated,along with several master regulatorygenes. During the mid-embryonic stage,there was continued expression of masterregulatory genes and a marked productionof extracellular matrix genes, which arekey in determining the shape and activitiesof the cell. In newborn rats, the researcherswitnessed upregulation of a number ofgenes thought to be involved in theresponse to the stress of birth. [Staurt, R.O.et al. (2001) Proc. Natl. Acad. Sci. U. S. A.98, 5649–5654] PL

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Photograph courtesy of Geoff Crawford/Tearfund.