The bHLH gene Hes6, an inhibitor of Hes1, promotes neuronal differentiation.
We have isolated the basic helix-loop-helix (bHLH) gene Hes6, a novel member of the family of mammalian homologues of Drosophila hairy and Enhancer of split. Hes6 is expressed by both undifferentiated and differentiated cells, unlike Hes1, which is expressed only by the former cells. Hes6 alone does not bind to the DNA but suppresses Hes1 from repressing transcription. In addition, Hes6 suppresses Hes1 from inhibiting Mash1-E47 heterodimer and thereby enables Mash1 and E47 to upregulate transcription in the presence of Hes1. Furthermore, misexpression of Hes6 with retrovirus in the developing retina promotes rod photoreceptor differentiation, like Mash1, in sharp contrast to Hes1, which inhibits cell differentiation. These results suggest that Hes6 is an inhibitor of Hes1, supports Mash1 activity and promotes cell differentiation. Mutation analysis revealed that Hes1- and Hes6-specific functions are, at least in part, interchangeable by alteration of the loop region, suggesting that the loop is not simply a nonfunctional spacer but plays an important role in the specific functions.
Bae
S
S
Institute for Virus Research, Kyoto University, Shogoin-Kawahara, Sakyo-ku, Kyoto 606-8507, Japan.
Bessho
Y
Y
Hojo
M
M
Kageyama
R
R
D016475:3T3 Cells; D000595:Amino Acid Sequence; D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins; D001921:Brain / Q000378:metabolism; D019556:COS Cells; D002454:Cell Differentiation; D018076:DNA, Complementary / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D020224:Expressed Sequence Tags; D015723:Gene Library; D018257:Helix-Loop-Helix Motifs; D018398:Homeodomain Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D009154:Mutation; D009474:Neurons / Q000166:cytology*; D010957:Plasmids; D012097:Repressor Proteins; D012160:Retina / Q000378:metabolism; D017948:Retinal Rod Photoreceptor Cells / Q000196:embryology; D012190:Retroviridae / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D051820:TCF Transcription Factors; D013997:Time Factors; D014018:Tissue Distribution; D058125:Transcription Factor 7-Like 1 Protein; D000072056:Transcription Factor HES-1; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism / Q000502:physiology*; D014158:Transcription, Genetic; D014162:Transfection; D015854:Up-Regulation
D051792:Basic Helix-Loop-Helix Proteins; D018076:DNA, Complementary; D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; D012097:Repressor Proteins; D051820:TCF Transcription Factors; D058125:Transcription Factor 7-Like 1 Protein; D000072056:Transcription Factor HES-1; D014157:Transcription Factors; C065500:ASCL1 protein, human; C499317:Ascl1 protein, mouse; C411859:HES6 protein, human; C489734:Hes1 protein, mouse; C486570:Hes6 protein, mouse; C544912:TCF7L1 protein, human; C544913:Tcf7l1 protein, mouse; C078493:HES1 protein, human