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Background  Transcription factor Cdx4 and transcriptional coregulator menin are essential for  Hoxa9  expression and normal hematopoiesis. However, the precise mechanism underlying  Hoxa9  regulation is not clear.    Methods and Findings  Here, we show that the expression level of  Hoxa9  is correlated with the location of increased trimethylated histone 3 lysine 4 (H3K4M3). The active and repressive histone modifications co-exist along the  Hoxa9  regulatory region. We further demonstrate that both Cdx4 and menin bind to the same regulatory region at the  Hoxa9  locus in vivo, and co-activate the reporter gene driven by the  Hoxa9 cis -elements that contain Cdx4 binding sites. Ablation of menin abrogates Cdx4 access to the chromatin target and significantly reduces both active and repressive histone H3 modifications in the  Hoxa9  locus.    Conclusion  These results suggest a functional link among Cdx4, menin and histone modifications in  Hoxa9  regulation in hematopoietic cells.

Cdx4 and Menin Co-Regulate Hoxa9 Expression in Hematopoietic Cells