The vHNF1 homeodomain protein establishes early rhombomere identity by direct regulation of Kreisler expression.
The early transcriptional hierarchy that subdivides the vertebrate hindbrain into seven to eight segments, the rhombomeres (r1-r8), is largely unknown. The Kreisler (MafB, Krml1, Val) gene is earliest gene expressed in an r5/r6-restricted manner and is essential for r5 and r6 development. We have identified the S5 regulatory element that directs early Kreisler expression in the future r5/r6 domain in 0-10 somite stage embryos. variant Hepatocyte Nuclear Factor 1 (vHNF1/HNF1beta/LF-3B) is transiently expressed in the r5/r6 domain of 0-10 somite stage embryos and a vHNF1binding site within this element is essential but not sufficient for r5/r6-specific expression. Thus, early inductive events that initiate Kreisler expression are clearly distinct from later-acting ones that modulate its expression levels. This site and some of the surrounding sequences are evolutionarily conserved in the genomic DNA upstream of the Kreisler gene among species as divergent as mouse, humans, and chickens. This provides the first evidence of a direct requirement for vHNF1 in initiation of Kreisler expression, suggests that the role of vHNF1 is evolutionarily conserved, and indicates that vHNF1 collaborates with other transcription factors, which independently bind to the S5 regulatory region, to establish the r5/r6 domain.
Kim
Florence A
FA
Samuel Lunenfeld Research Institute, Mt Sinai Hospital, 600 University Avenue, Toronto, Ont., Canada.
Sing l
Angela
A
Kaneko
Tomomi
T
Bieman
Melissa
M
Stallwood
Nicole
N
Sadl
Virginia S
VS
Cordes
Sabine P
SP
D000818:Animals; D001483:Base Sequence; D001665:Binding Sites / Q000235:genetics; D002454:Cell Differentiation / Q000235:genetics; D017124:Conserved Sequence; D004742:Enhancer Elements, Genetic; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D014644:Genetic Variation; D051537:Hepatocyte Nuclear Factor 1 / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D018398:Homeodomain Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D006801:Humans; D051258:MafB Transcription Factor / Q000096:biosynthesis* / Q000235:genetics*; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D012249:Rhombencephalon / Q000166:cytology / Q000196:embryology* / Q000378:metabolism
D018398:Homeodomain Proteins; D051258:MafB Transcription Factor; C490406:Mafb protein, mouse; D051537:Hepatocyte Nuclear Factor 1