Two DNA binding domains of MGA act I combination to suppress abnormal activation of meiosis-related genes in mouse ESCs.

MGA plays important roles in DNA binding as well as constructing the complex as a scaffolding component. MGA bears two distinct DNA-binding domains termed bHLHZ and T-box. Both DNA binding domain of MGA are involved in repression of rather distinct sets of genes in ESCs. But, substantial numbers of meiosis-related genes are included in both gene sets. Notably, Meiosin gene that plays essential roles in meiotic entry in collaboration with Stra8 is included among genes regulated exclusively by the bHLHZ domain, suggesting that the negative regulation by MGA resides upstream of positive regulation by STRA8/MEIOSIN complex within the transcriptional network of meiotic onset. Dox-treated Max-KO ESCs bearing exogenous Max cDNA whose expression is under the control of tet-off system or two different Mga mutant ESCs producing MGA protein lacking either bHLHZ or T-box domain that were cultured under conventional culture condition for mouse ESCs were used for RNA sources. These RNAs were used to compare their global expression profiles by DNA microarray analyses. Samples, from Dox-untreated Max cKO ESCs or empty virus-infected ESCs under conventional culture condition were used as reference samples.