Ash2l interacts with Tbx1 and is required during early embryogenesis

Experimental Biology and Medicine - Tập 235 Số 5 - Trang 569-576 - 2010
Jason Z. Stoller1,2, Li Huang3, Cheryl C. Tan4,5,6, Facan Huang7, Diane Zhou1, Jifu Yang1, Bruce D. Gelb5,8,6, Jonathan A. Epstein1
1Department of Cell and Developmental Biology and the Penn Cardiovascular Institute
2Department of Pediatrics, Division of Neonatology, Children's Hospital of Philadelphia
3Department of Animal Biology, University of Pennsylvania, Philadelphia, PA 19104
4Department of Biological Chemistry, University of California, Los Angeles, Los Angeles, CA 90095, USA
5Department of Center for Molecular Cardiology, Mount Sinai School of Medicine, New York, NY 10029
6Department of Pediatrics
7Huagene Biosciences Ltd, Futian Avenue, Sanming, Fujian 366100, People's Republic of China
8Department of Genetics and Genomic Sciences, Mount Sinai School of Medicine, New York, NY 10029 USA

Tóm tắt

TBX1 encodes a DNA binding transcription factor that is commonly deleted in human DiGeorge syndrome and plays an important role in heart development. Mechanisms of Tbx1 function, such as Tbx1 interacting regulatory proteins and transcriptional target specificity, are largely unknown. Ash2l is the mammalian homolog of Drosophila Ash2 (absent small homeotic 2) and is a core component of a multimeric histone methyltransferase complex that epigenetically regulates transcription via methylation of histone lysine residues. We undertook an unbiased yeast two-hybrid screen to look for functionally relevant Tbx1-interacting proteins and report a physical and functional interaction between Tbx1 and Ash2l. Tbx1 interacts with Ash2l in both yeast and mammalian cells and Ash2l acts as a transcriptional co-activator in luciferase reporter assays. Expression analysis shows that Tbx1 and Ash2l have overlapping mRNA and protein expression patterns during development. By generating an Ash2l knockout mouse utilizing gene-trap technology, we show that although Ash2l heterozygous mice are normal, Ash2l-null embryos die early during gestation. Thus, Ash2l is required for the earliest stages of embryogenesis. Furthermore, our finding of a physical interaction between Tbx1 and Ash2l suggest that at least some functions of Tbx1 may be mediated by direct interactions with a histone methyltransferase complex.

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Experimental Biology and Medicine

Tập 235 Số 5

569-576

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