ZFIN ID: ZDB-PUB-120430-12
Zebrafish globin switching occurs in two developmental stages and is controlled by the LCR
Ganis, J.J., Hsia, N., Trompouki, E., de Jong, J.L., Dibiase, A., Lambert, J.S., Jia, Z., Sabo, P.J., Weaver, M., Sandstrom, R., Stamatoyannopoulos, J.A., Zhou, Y., and Zon, L.I.
Date: 2012
Source: Developmental Biology   366(2): 185-194 (Journal)
Registered Authors: de Jong, Jill, Hsia, Nelson, Zhou, Yi, Zon, Leonard I.
Keywords: zebrafish, erythropoiesis, glopbin switching, locus control region
Microarrays: GEO:GSE35874, GEO:GSE35875, GEO:GSE35895
MeSH Terms:
  • Animals
  • Embryo, Nonmammalian/embryology
  • Embryo, Nonmammalian/physiology
  • GATA1 Transcription Factor/genetics
  • Gene Expression Regulation, Developmental
  • Genes, Switch
  • Globins/genetics*
  • Locus Control Region/genetics*
  • NF-E2 Transcription Factor, p45 Subunit/genetics
  • Zebrafish/embryology
  • Zebrafish/genetics*
  • Zebrafish Proteins/genetics
PubMed: 22537494 Full text @ Dev. Biol.

Globin gene switching is a complex, highly regulated process allowing expression of distinct globin genes at specific developmental stages. Here, for the first time, we have characterized all of the zebrafish globins based on the completed genomic sequence. Two distinct chromosomal loci, termed major (chromosome 3) and minor (chromosome 12), harbor the globin genes containing α/β pairs in a 52–32 to 32–52 orientation. Both these loci share synteny with the mammalian α-globin locus. Zebrafish globin expression was assayed during development and demonstrated two globin switches, similar to human development. A conserved regulatory element, the locus control region (LCR), was revealed by analyzing DNase I hypersensitive sites, H3K4 trimethylation marks and GATA1 binding sites. Surprisingly, the position of these sites with relation to the globin genes is evolutionarily conserved, despite a lack of overall sequence conservation. Motifs within the zebrafish LCR include CACCC, GATA, and NFE2 sites, suggesting functional interactions with known transcription factors but not the same LCR architecture. Functional homology to the mammalian α-LCR MCS-R2 region was confirmed by robust and specific reporter expression in erythrocytes of transgenic zebrafish. Our studies provide a comprehensive characterization of the zebrafish globin loci and clarify the regulation of globin switching.