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Kashyap Chhatbar, Raphaël Pantier, Timo Quante, Konstantina Skourti-Stathaki, Jim Selfridge, Adrian Bird (Wellcome Centre for Cell Biology, University of Edinburgh, Michael Swann Building, Max Born Crescent, EDINBURGH, EH9 3BF, U. K.)
Vertebrate genomes are segmented to give multi-gene domains that differ with respect to DNA base composition. Here we test the hypothesis that base compositional stratification is interpreted by DNA binding proteins that recognise runs of A/T bases. We found that the stem cell-specific factor SALL4 preferentially senses A/T content to bring about blanket inhibition of genes that promote neuronal differentiation. An A/T binding zinc finger cluster is essential to prevent inappropriate stem cell differentiation, whereas other zinc finger clusters are dispensable. We conclude that base composition is not a passive by-product of genome evolution, but is read as a signal to facilitate control of developmental gene expression programmes and hence cell fate.