Regulation of Hoxc-8 during mouse embryonic development: identification and characterization of critical elements involved in early neural tube expression.
We have characterized cis-acting elements that direct the early phase of Hoxc-8 expression using reporter gene analysis in transgenic mice. By deletion we show that a 135 bp DNA fragment, located approximately 3 kb upstream of the coding region of Hoxc-8, is capable of directing posterior neural tube expression. This early neural tube (ENT) enhancer consists of four separate elements, designated A, B, C and D, whose nucleotide sequences are similar to binding sites of known transcription factors. Nucleotide substitutions suggest that element A is an essential component of the ENT enhancer. However element A by itself is incapable of directing neural tube expression. This element requires interactions at any two of the other three elements, B, C or D. Thus, the components of the ENT enhancer direct neural tube expression in an interdependent manner. We propose that Hoxc-8 is activated in the neural tube by combinatorial interactions among several proteins acting within a small region. Our transgenic analyses provide a means to identify transcription factors that regulate Hoxc-8 expression during embryogenesis.
Shashikant
C S
CS
Department of Biology, Yale University, New Haven CT 06520, USA.
Bieberich
C J
CJ
Belting
H G
HG
Wang
J C
JC
Borbély
M A
MA
Ruddle
F H
FH
D000818:Animals; D001483:Base Sequence; D002490:Central Nervous System / Q000196:embryology*; D004252:DNA Mutational Analysis; D017931:DNA Primers / Q000235:genetics; D018507:Gene Expression Regulation, Developmental; D005801:Genes, Homeobox; D017930:Genes, Reporter; D018398:Homeodomain Proteins / Q000235:genetics*; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D009024:Morphogenesis
D017931:DNA Primers; D018398:Homeodomain Proteins