TRENDS in Genetics Vol.18 No.4 April 2002184 News&CommentNews&Comment

Letter

must be turned off,’ said Strahl. Set2 mightbe such an ‘off switch’ for gene regulation in cells. In addition, this modification couldbe part of an emerging ‘molecular code’ of histone modifications that ultimatelyregulate these developmental processes.(Strahl, B.D. et al. [2002] Mol. Cell. Biol.22, 1298–1306) PL

Reliable information ongenetic diseasesThe National Human Genome ResearchInstitute (NHGRI) and the National Institutesof Health’s Office of Rare Diseases (ORD)have launched a new information centerthat delivers free and immediate access toaccurate, reliable information about geneticand rare diseases to patients and theirfamilies. The Genetic and Rare DiseasesInformation Center provides informationspecialists to answer questions by phone,e-mail, fax and mail. “I am delighted we canprovide a resource that should be of greatbenefit to individuals with genetic and rarediseases and their families,” said FrancisCollins, director of NHGRI. “Valid andaccessible information about theseconditions is hard to find.” For moreinformation, e-mail: gardinfo@nih.gov.

In the UK, the Genetic Interest Group, analliance of charities and support groups forfamilies with genetic disorders, providesinformation on scientific advances and theirimpact on those affected by genetic disease.The GIG website (http://www.gig.org.uk) is about to embark on an ambitiousdevelopment that will allow those with the conditions to express their views andopinions directly through the use of videoclips and other materials. This aims to ensurethat the voice of the patients and theirfamilies is given due weight in the debateabout the implication of new knowledgestemming from research and development inthe field of human genetics. HD and AK

International effort tosequence tree genome

Cottonwoods,hybrid poplars andaspens could have arole in improving theenvironment anddisplacing importedoil, but first

scientists from the US Department of Energy(DOE), Oak Ridge National Laboratory(TN, USA) and around the world have tosequence the Populus genome. The choice ofPopulus as the first tree genome to sequenceis due largely to their rapid growth rate, smallgenome size and widespread use in areas ofinterest to the forest industry and DOE. ‘Thiseffort will furnish scientists both in thiscountry and abroad with an unprecedentedmolecular ‘parts list’ for a tree,’ said JerryTuskan, a researcher in ORNL’sEnvironmental Sciences Division. ‘Such a listwill provide the scientific community with acatalog of genes, knowledge as to what thesegenes do in trees and an exciting opportunityto better understand how trees grow.’(http://www.ornl.gov/news). NJ

Thermophilic universalancestor?What was the last universal commonancestor (LUCA)? Massimo Di Giulio hasexamined whether LUCA was a mesophile ora thermophile, using maximum parsimonyand likelihood methods. By exploiting acorrelation between the optimal growthtemperature of organisms and a thermophilyindex based on how amino acids can enterthermophilic and hyperthermophilicproteins, Di Giulio reconstructed all possiblephylogenetic tree toplogies derived fromsmall subunit ribosomal RNA. From thisanalysis, the thermophily index derived from

all the reconstructed LUCA sequences allgrouped into the thermophilic andhyperthermophilic sequences supporting the hypothesis that LUCA was either athermophile or a hyperthemophile. (DiGiulio, M. [2001] Gene, 281, 11–17) SG

Probing the nucleolus withproteomicsNucleoli have a surprisingly large proteincomplexity and could perform functionsother than their known role in ribosomesubunit biogenesis. These are theconclusions of a group of researchersheaded by Angus Lamond, who used acombination of protein separationtechniques and mass spectrometry coupledwith sequence database searches to identify271 proteins within the nucleolus. Of these,80 (30%), are novel or uncharacterized genes.Several other factors were identified that hadnot been associated with a nucleolar functionuntil now. In addition, treating cells with an inhibitor of transcription caused theenrichment of a subset of 11 proteins in thenucleoli, indicating that nucleolar proteinsare responsive to the metabolic state of thecell. This is the largest proteomic analysis ofa single organelle to date, and it shows thedynamic nature of this structure. Theseresults demonstrate the power of theproteomic approach to probe complexbiological questions. (Andersen, J.S. et al.[2002] Curr. Biol. 12, 1–11) SG

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A common element inepidermal expression?The sequencing of the human genome hasprovided a vast amount of information forthose who study the way in which genesare regulated at the transcriptional level.In principle, the sequence of every

promoter and enhancer of every genecould allow potential sites fortranscription factor interactions to beidentified. These sites are typically verysmall however, usually between four and 14 basepairs (bp), so it is generally not possible to predict their existencesimply by examining the sequence. TheDNA-binding requirements of a specific

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Helen Dell tig@current-trends.comSteven G. Gray Steven.Gray@vai.orgNorman A. Johnson

njohnson@ent.umass.eduAlistair Kent alastairkent@gig.org.ukPetros Ligoxygakis

P.Ligoxygakis@ibmc.u-strasbg.frAkhilesh Pandey pandey@cebi.sdu.dk

TRENDS in Genetics Vol.18 No.4 April 2002 185News&CommentNews&Comment

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transcription factor must instead bedetermined by experiment.

An alternative approach is to isolatevery short segments of promoter orenhancer regions, link them to a minimalpromoter and see whether they can drivethe correct expression of a reporter gene.This approach was used to identify a17-bp sequence (W5aE) in the Wnt-5apromoter that can drive Wnt-5aexpression in the ectodermal cells of theearly embryo [1]. The W5aE sequenceactually contains a consensus binding site for the transcription factor Otx2,resulting in the exclusion of Wnt-5aexpression from the most-anteriorectoderm, where Otx2 is expressed. When a single nucleotide is changed that blocks Otx2 binding, W5aE is able to drive the pan-ectodermal expression of a reporter gene. Intriguingly, thisaltered W5aE sequence actually occurs in the endogenous promoter of the gene encoding keratin (called KerA1),

in the same orientation andapproximately the same position relative to the translation start site of the encoded mRNA.

Of course, KerA1 and Wnt-5a are onlytwo of a very large number of genes thatare expressed mostly or wholly in theectoderm. Sequencing of the 1q region of human chromosome 21 has revealed a region (the epidermal differentiationcomplex; EDC), in which the majority of genes are expressed exclusively in epidermal cells, where they haveimportant developmental and structural functions [2,3]. The EDCcovers about 2.5 Mb, containing at least 25 genes, and it can be split bothfunctionally and physically into two main groups (Fig. 1). One of thesecontains members of the S100 genefamily, which are characterized by thepresence of ‘EF-hand’ calcium-bindingmotifs. The other group is the SPRRgenes, all of which encode short,

proline-rich peptides. In addition to these families, there are other geneswithin the complex that are alsoexpressed exclusively in the epidermis,including the RNA-binding proteinsADAR1 and TDRKH, Hax1 (which binds histone-like proteins), and afurther series of related genes (NICE1–5) that have no known function.The exact nature of the control thatrestricts the expression of the EDC genes to the epidermis is unknown,although the chromatin of this region is uniformly controlled to be either open or closed [4–6].

Do EDC genes contain the W5aEsequence that drives the ectodermalspecific expression of Wnt-5a? Comparing the sequence of the knownEDC members suggests that the majoritydo (Table 1). Furthermore, thesesequences are in the same orientation andrelative position (i.e. within 600 bp of thetranslation start site) as the W5aE motifin both Wnt-5a and KerA1. It is temptingto speculate then that the W5aE motifmight have a universal role in directingepidermal expression; it will beinteresting to see whether future studiesbear this out.

Richard Morgan

Dept of Anatomy and DevelopmentalBiology, St George’s Hospital MedicalSchool, Cranmer Terrace, London, UK SW17 0RE.e-mail: rmorgan@sghms.ac.uk

References

1 Morgan, R. et al. (1999) A conserved 30 base pairelement in the Wnt-5a promoter is sufficient bothto drive its early embryonic expression and tomediate its repression by otx2. Mech. Dev.85, 97–102

2 Mischke, D. et al. (1996) Genes encodingstructural proteins of epidermal cornification andS100 calcium-binding proteins form a genecomplex (‘epidermal differentiation complex’) onhuman chromosome 1q21. J. Invest. Dermatol.106, 989–992

3 Maestrini, E. et al. (1996) A molecular defect inloricrin, the major component of the cornified cellenvelope, underlies Vohwinkel’s syndrome. Nat.Genet. 13, 70–77

4 Marenholz, I. et al. (1996) Genetic analysis of theepidermal differentiation complex (EDC) onhuman chromosome 1q21: chromosomalorientation, new markers, and a 6-Mb YAC contig.Genomics 37, 295–302

5 Lioumi, M. et al. (1998) High-resolution YACfragmentation map of 1q21. Genomics 15, 200–208

6 Marshall, D. et al. (2001) Differentially expressedlate constituents of the epidermal cornifiedenvelope. Proc. Natl. Acad. Sci. U. S. A.98, 13031–13036

TRENDS in Genetics

0 0.5 1 1.5 2 2.5 Mb

S10

0A10

TH

H

FLG

IVL

SP

RR

3

SP

RR

1B

SP

RR

2A

LOR

S100A

9 8 7 6 2 1…

Fig. 1. Map of the human epidermal differentiation complex (EDC) in 1q21. Genes belonging to the same familyare shown in the same colour. The S100A genes 1–9 are very closely clustered and the number of each is shownbelow ‘S100A’. Not all the EDC genes are shown, as their precise location within the complex is yet to bedetermined. THH, trichohyalin; FLG, profilaggrin; IVL, involucrin; LOR, locricin; Mb, million basepairs.Adapted from Ref. [2].

Table 1. Identification of putative W5aE elements in the epidermal differentiation

complex (EDC) genes by sequence alignmenta

Gene Match to consensus Accession No. Function

Wnt-5a CTCxx-CCCTGGATxAAC L19716 SignallingKerA1 CTCxxxCCCTGGATxAAC X04804 StructuralHax1 CTCxxxCCCTGGATxAxC XM_001403 Binds HS1 proteinTDRKH CTxxxxCCCTGGxxxxAC NM_006862 Binds RNANICE3 CTCxxxCCCTGGAxxxAC AJ243664 ?NICE4 CTxxxxCCCTGGxxxAAC AJ243668 ?NICE5 CTxxxxCCCxGxTxxAAC AJ243666 ?ECM1 CTCxx-CCCTGGAxxxxC NM_022664 Structuralaf11 CTxxxxCCCTGGAxxxxC AF119121 Binds RNASPRR4 TCxxxCCCTGxxTxAAC AF335109 StructuralSPRR3 CxxxCCCTGxxxxAAC AJ243667 StructuralXP5 CTxxxxCCCTGGAx-AAC NM_014357 ?XP32 CTx---CCCTGGAT-A-C AF005081 ?ivl CTxxxxCCCTGGATxAxC NM_005547 StructuralFilagrin CTCxxxxCCTGGAx-AAC L01090 StructuralADAR1 CTCxxxCCCTGGA AF052566 Deaminates RNA

aNucleotides shown in boldface are conserved between the sequence identified in each EDC gene and that in theW5aE element of Wnt-5a. x, a non-conserved nucleotide; –, a gap introduced to aid the alignment. The referencefor each gene can be found via the GenBank accession number.