Transcriptional regulation of an axonemal central apparatus gene, sperm-associated antigen 6, by a SRY-related high mobility group transcription factor, S-SOX5.
SOX5 is a transcription factor with homology to the high mobility group box region of the testis-determining factor, SRY. Both the mouse and human SOX5 genes encode a 48-kDa SOX5 protein (S-SOX5) that is only present in tissues containing cells with motile cilia/flagella. The mammalian sperm-associated antigen 6 gene (SPAG6) encodes an axoneme central apparatus protein. Because human and mouse SPAG6 gene promoters contain multiple potential binding sites for SOX5, SPAG6 gene regulation by S-SOX5 was investigated in BEAS-2B cells, a line derived from human bronchial cells. Like FOXJ1, a transcription factor known to be essential for motile ciliogenesis, S-SOX5 stimulated mouse and human SPAG6 promoter function in BEAS-2B cells, but the effect was abrogated when the SOX5 binding sites were mutated or deleted. S-SOX5 and FOXJ1 functioned cooperatively in stimulating SPAG6 promoter activity. The SPAG6 message was up-regulated when S-SOX5 was overexpressed in BEAS-2B cells, and silencing of S-SOX5 by RNA interference down-regulated SPAG6 transcripts. Chromatin immunoprecipitation and EMSA experiments demonstrated that S-SOX5 associates with the SPAG6 promoter directly. The present study demonstrates that SPAG6 is a S-SOX5 target gene, indicating a key role for S-SOX5 in the formation and function of motile cilia.
Kiselak
Elizabeth Anne
EA
Department of Obstetrics and Gynecology, Virginia Commonwealth University, Richmond, Virginia 23298, USA.
Shen
Xuening
X
Song
Jingmei
J
Gude
David Roberto
DR
Wang
Jiannan
J
Brody
Steven L
SL
Strauss
Jerome F
JF
Zhang
Zhibing
Z
D000818:Animals; D002460:Cell Line; D002923:Cilia / Q000235:genetics / Q000378:metabolism*; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism; D006801:Humans; D051379:Mice; D008868:Microtubule Proteins / Q000235:genetics / Q000378:metabolism*; D020218:Response Elements / Q000502:physiology*; D055755:SOXD Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic / Q000502:physiology*
C106349:FOXJ1 protein, human; C481963:FOXJ1 protein, mouse; D051858:Forkhead Transcription Factors; D008868:Microtubule Proteins; C490301:SOX5 protein, human; D055755:SOXD Transcription Factors; C400106:SPAG6 protein, human; C504274:SPAG6 protein, mouse; C089186:Sox5 protein, mouse