GATA-1 is a potential repressor of anti-Müllerian hormone expression during the establishment of puberty in the mouse.
Anti-Müllerian hormone (AMH), also known as Müllerian inhibiting substance (MIS), is one of the earliest and best-known markers of Sertoli cell differentiation and is expressed until around puberty. The present study is aimed at the better understanding of the molecular pathways involved in testicular development and establishment of adult functions with regards to AMH regulation. We found, within the mouse AMH promoter, putative GATA motifs (A/T)GATA(A/G), known to be specifically bound by members of the GATA transcription factor family. We then carried out RNase protection assays and immunohistochemical techniques aimed at comparing precisely the chronological expression patterns of AMH and GATA-1, this latter being expressed in the testis after birth. Using both approaches we found an inverse and close relationship between AMH and GATA-1 mRNA and protein expression during the pre-pubertal period. These results allowed us to define a transitory 4-5-day period, starting from 3 dpp when both proteins are heterogeneously expressed in Sertoli cells and showed that the appearance of GATA-1 is associated with the decrease of AMH expression in these cells. Furthermore DNA-protein interaction in in vitro studies showed first that GATA-1 binds with various affinities on sites found in the AMH promoter and second that the proximity of the two strongest affinity sites leads to a synergistic binding effect. Altogether, the present study suggests that GATA-1 participates in AMH gene repression during the pre-pubertal period.
Beau
C
C
GERM/INSERM U. 435, Université de Rennes 1, Rennes, Bretagne, France.
Rauch
M
M
Joulin
V
V
Jégou
B
B
Guerrier
D
D
D000818:Animals; D054304:Anti-Mullerian Hormone; D001483:Base Sequence; D001665:Binding Sites; D002417:Cattle; D017124:Conserved Sequence; D018076:DNA, Complementary; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D050981:Erythroid-Specific DNA-Binding Factors; D050982:GATA1 Transcription Factor; D050991:GATA4 Transcription Factor; D005786:Gene Expression Regulation; D006023:Glycoproteins; D006131:Growth Inhibitors / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D011627:Puberty; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D013735:Testicular Hormones / Q000235:genetics* / Q000378:metabolism; D013997:Time Factors; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
D018076:DNA, Complementary; D004268:DNA-Binding Proteins; D050981:Erythroid-Specific DNA-Binding Factors; D050982:GATA1 Transcription Factor; C494688:GATA1 protein, human; D050991:GATA4 Transcription Factor; C494689:Gata1 protein, mouse; C494690:Gata1 protein, rat; D006023:Glycoproteins; D006131:Growth Inhibitors; D011993:Recombinant Fusion Proteins; D012097:Repressor Proteins; D013735:Testicular Hormones; D014157:Transcription Factors; D054304:Anti-Mullerian Hormone