A conserved E2F6-binding element in murine meiosis-specific gene promoters.
During gametogenesis, germ cells must undergo meiosis in order to become viable haploid gametes. Successful completion of this process is dependent upon the expression of genes whose protein products function specifically in meiosis. Failure to express these genes in meiotic cells often results in infertility, whereas aberrant expression in somatic cells may lead to mitotic catastrophe. The mechanisms responsible for regulating the timely expression of meiosis-specific genes have not been fully elucidated. Here we demonstrate that E2F6, a member of the E2F family of transcription factors, is essential for the repression of the newly identified meiosis-specific gene, Slc25a31 (also known as Ant4, Aac4), in somatic cells. This discovery, along with previous studies, prompted us to investigate the role of E2F6 in the regulation of meiosis-specific genes in general. Interestingly, the core E2F6-binding element (TCCCGC) was highly conserved in the proximal promoter regions of 19 out of 24 (79.2%) meiosis-specific genes. This was significantly higher than the frequency found in the promoters of all mouse genes (15.4%). In the absence of E2F6, only a portion of these meiosis-specific genes was derepressed in somatic cells. However, endogenous E2F6 bound to the promoters of these meiosis-specific genes regardless of whether they required E2F6 for their repression in somatic cells. Further, E2F6 overexpression was capable of reducing their transcription. These findings indicate that E2F6 possesses a broad ability to bind to and regulate the meiosis-specific gene population.
Kehoe
Sarah M
SM
Department of Pathology, University of Florida College of Medicine, Gainesville, Florida 32610, USA.
Oka
Masahiro
M
Hankowski
Katherine E
KE
Reichert
Nina
N
Garcia
Sandra
S
McCarrey
John R
JR
Gaubatz
Stefan
S
Terada
Naohiro
N
D000818:Animals; D001483:Base Sequence; D017124:Conserved Sequence; D050701:E2F6 Transcription Factor / Q000378:metabolism*; D005786:Gene Expression Regulation; D008540:Meiosis; D026901:Membrane Transport Proteins / Q000235:genetics*; D051379:Mice; D008969:Molecular Sequence Data; D041681:NIH 3T3 Cells; D011401:Promoter Regions, Genetic
D050701:E2F6 Transcription Factor; C111236:E2f6 protein, mouse; D026901:Membrane Transport Proteins; C524039:adenine nucleotide translocase 4, mouse