title: E4BP4 is a cardiac survival factor and essential for embryonic heart development.
abstract: The bZIP transcription factor E4BP4, has been demonstrated to be a survival factor in pro-B lymphocytes. GATA factors play important roles in transducing the IL-3 survival signal and transactivating the downstream survival gene, E4BP4. In heart, GATA sites are essential for proper transcription of several cardiac genes, and GATA-4 is a mediator of cardiomyocyte survival. However, the role E4BP4 plays in heart is still poorly understood. In this study, Dot-blot hybridization assays using Dig-labeled RNA probes revealed that the E4BP4 gene was expressed in cardiac tissue from several species including, monkey, dog, rabbit, and human. Western blot analysis showed that the E4BP4 protein was consistently present in all of these four species. Furthermore, immunohistochemistry revealed that the E4BP4 protein was overexpressed in diseased heart tissue in comparison with normal heart tissue. In addition, the overexpression of E4BP4 in vitro activated cell survival signaling pathway of cardiomyocytes. At last, siRNA-mediated knock down of E4BP4 in zebrafish resulted in malformed looping of the embryonic heart tube and decreased heart beating. Based on these results, we conclude that E4BP4 plays as a survival factor in heart and E4BP4 is essential for proper embryonic heart development.
authors.affiliation: Department of Veterinary Medicine, National Chung-Hsing University, No.250, Kuo-Kuang Road, 402 Taichung, Taiwan.
authors.forename: Yi-Jiun
authors.initials: YJ
authors.lastname: Weng
authors.forename: Dennis Jine-Yuan
authors.initials: DJ
authors.lastname: Hsieh
authors.forename: Wei-Wen
authors.initials: WW
authors.lastname: Kuo
authors.forename: Tung-Yuan
authors.initials: TY
authors.lastname: Lai
authors.forename: Hsi-Hsien
authors.initials: HH
authors.lastname: Hsu
authors.forename: Chang-Hai
authors.initials: CH
authors.lastname: Tsai
authors.forename: Fuu-Jen
authors.initials: FJ
authors.lastname: Tsai
authors.forename: Ding-Yu
authors.initials: DY
authors.lastname: Lin
authors.forename: James A
authors.initials: JA
authors.lastname: Lin
authors.forename: Chih-Yang
authors.initials: CY
authors.lastname: Huang
authors.forename: Kwong-Chung
authors.initials: KC
authors.lastname: Tung
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D050976:Basic-Leucine Zipper Transcription Factors / Q000235:genetics / Q000378:metabolism*; D015153:Blotting, Western; D002470:Cell Survival; D002478:Cells, Cultured; D004285:Dogs; D018507:Gene Expression Regulation, Developmental; D055785:Gene Knockdown Techniques; D000882:Haplorhini; D006321:Heart / Q000196:embryology*; D006801:Humans; D007150:Immunohistochemistry; D008969:Molecular Sequence Data; D009024:Morphogenesis; D032383:Myocytes, Cardiac / Q000378:metabolism*; D009693:Nucleic Acid Hybridization; D034622:RNA Interference; D011817:Rabbits; D015398:Signal Transduction; D014162:Transfection; D015027:Zebrafish; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D050976:Basic-Leucine Zipper Transcription Factors; C497440:NFIL3 protein, human; D029961:Zebrafish Proteins