E4BP4 is a cardiac survival factor and essential for embryonic heart development.
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.
Weng
Yi-Jiun
YJ
Department of Veterinary Medicine, National Chung-Hsing University, No.250, Kuo-Kuang Road, 402 Taichung, Taiwan.
Hsieh
Dennis Jine-Yuan
DJ
Kuo
Wei-Wen
WW
Lai
Tung-Yuan
TY
Hsu
Hsi-Hsien
HH
Tsai
Chang-Hai
CH
Tsai
Fuu-Jen
FJ
Lin
Ding-Yu
DY
Lin
James A
JA
Huang
Chih-Yang
CY
Tung
Kwong-Chung
KC
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*
D050976:Basic-Leucine Zipper Transcription Factors; C497440:NFIL3 protein, human; D029961:Zebrafish Proteins