PMID- 12517812 OWN - NLM STAT- MEDLINE DCOM- 20030521 LR - 20210206 IS - 0006-4971 (Print) IS - 0006-4971 (Linking) VI - 101 IP - 7 DP - 2003 Apr 1 TI - Functional and comparative analysis of globin loci in pufferfish and humans. PG - 2842-9 AB - To further our understanding of the regulation of vertebrate globin loci, we have isolated cosmids containing alpha- and beta-globin genes from the pufferfish Fugu rubripes. By DNA fluorescence in situ hybridization (FISH) analysis, we show that Fugu contains 2 distinct hemoglobin loci situated on separate chromosomes. One locus contains only alpha-globin genes (alpha-locus), whereas the other also contains a beta-globin gene (alpha beta-locus). This is the first poikilothermic species analyzed in which the physical linkage of the alpha- and beta-globin genes has been uncoupled, supporting a model in which the separation of the alpha- and beta-globin loci has occurred through duplication of a locus containing both types of genes. Surveys for transcription factor binding sites and DNaseI hypersensitive site mapping of the Fugu alpha beta-locus suggest that a strong distal locus control region regulating the activity of the globin genes, as found in mammalian beta-globin clusters, may not be present in the Fugu alpha beta-locus. Searching the human and mouse genome databases with the genes surrounding the pufferfish hemoglobin loci reveals that homologues of some of these genes are proximal to cytoglobin, a recently described novel member of the globin family. This provides evidence that duplication of the globin loci has occurred several times during evolution, resulting in the 5 human globin loci known to date, each encoding proteins with specific functions in specific cell types. FAU - Gillemans, Nynke AU - Gillemans N AD - MGC Department of Cell Biology, Erasmus MC, Rotterdam, The Netherlands. FAU - McMorrow, Tara AU - McMorrow T FAU - Tewari, Rita AU - Tewari R FAU - Wai, Albert W K AU - Wai AW FAU - Burgtorf, Carola AU - Burgtorf C FAU - Drabek, Dubravka AU - Drabek D FAU - Ventress, Nicki AU - Ventress N FAU - Langeveld, An AU - Langeveld A FAU - Higgs, Douglas AU - Higgs D FAU - Tan-Un, Kian AU - Tan-Un K FAU - Grosveld, Frank AU - Grosveld F FAU - Philipsen, Sjaak AU - Philipsen S LA - eng PT - Comparative Study PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20021127 PL - United States TA - Blood JT - Blood JID - 7603509 RN - 9004-22-2 (Globins) SB - IM MH - Animals MH - Consensus Sequence MH - Erythrocytes MH - *Evolution, Molecular MH - Gene Duplication MH - Gene Expression Regulation MH - Globins/biosynthesis/*genetics MH - Humans MH - Locus Control Region/genetics MH - Mice MH - Mice, Transgenic MH - Multigene Family/*genetics MH - Regulatory Sequences, Nucleic Acid MH - Sequence Homology, Nucleic Acid MH - Takifugu/*genetics EDAT- 2003/01/09 04:00 MHDA- 2003/05/22 05:00 CRDT- 2003/01/09 04:00 PHST- 2003/01/09 04:00 [pubmed] PHST- 2003/05/22 05:00 [medline] PHST- 2003/01/09 04:00 [entrez] AID - S0006-4971(20)51179-8 [pii] AID - 10.1182/blood-2002-09-2850 [doi] PST - ppublish SO - Blood. 2003 Apr 1;101(7):2842-9. doi: 10.1182/blood-2002-09-2850. Epub 2002 Nov 27.