The zinc finger gene Krox20 regulates HoxB2 (Hox2.8) during hindbrain segmentation.
The zinc finger gene Krox20 and many Hox homeobox genes are expressed in segment-restricted domains in the hindbrain. The restricted expression patterns appear before morphological segmentation, suggesting that these transcription factors may play an early role in the establishment and identity of rhombomeric segments. In this paper, we show that the HoxB2 (Hox2.8) gene is normally upregulated in rhombomeres (r) 3, 4, and 5, and we identify an enhancer region upstream of the gene that imposes r3/r5 expression in transgenic mice. This enhancer contains three Krox20-binding sites required in vitro for complex formation with Krox20 protein and in vivo for rhombomere-restricted expression. In transgenic mice, Krox20 expressed in ectopic domains can transactivate a reporter construct containing the HoxB2 r3/r5 enhancer. These data demonstrate that Krox20 is a part of the upstream transcriptional cascade that directly regulates HoxB2 expression during hindbrain segmentation.
Sham
M H
MH
MRC Laboratory of Eukaryotic Molecular Genetics, National Institute for Medical Research, The Ridgeway, Mill Hill, London.
Vesque
C
C
Nonchev
S
S
Marshall
H
H
Frain
M
M
Gupta
R D
RD
Whiting
J
J
Wilkinson
D
D
Charnay
P
P
Krumlauf
R
R
D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D001921:Brain / Q000196:embryology*; D004247:DNA / Q000235:genetics / Q000378:metabolism*; D015342:DNA Probes; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism*; D051767:Early Growth Response Protein 2; D005314:Embryonic and Fetal Development; D004742:Enhancer Elements, Genetic; D005801:Genes, Homeobox; D005809:Genes, Regulator; D017403:In Situ Hybridization; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D009838:Oligodeoxyribonucleotides; D015347:RNA Probes; D012249:Rhombencephalon / Q000196:embryology*; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism*; D016335:Zinc Fingers / Q000235:genetics*
D015342:DNA Probes; D004268:DNA-Binding Proteins; D051767:Early Growth Response Protein 2; C497327:Egr2 protein, mouse; D009838:Oligodeoxyribonucleotides; D015347:RNA Probes; D014157:Transcription Factors; D004247:DNA