WTIP interacts with ASXL2 and blocks ASXL2-mediated activation of retinoic acid signaling

• Published in: Biochemical and biophysical research communications Vol. 451; no. 1; pp. 101 - 106
• Main Authors: Khan, Farida F., Li, Yanyang, Balyan, Arjun, Wang, Q. Tian
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 15.08.2014
• Subjects: Animals; ASXL2; Carrier Proteins - genetics; Carrier Proteins - metabolism; Cells, Cultured; Epicardium; Heart development; HeLa Cells - drug effects; HeLa Cells - metabolism; Humans; Luciferases - genetics; Luciferases - metabolism; Mice; Pericardium - cytology; Pericardium - metabolism; Protein Structure, Tertiary; Repressor Proteins - genetics; Repressor Proteins - metabolism; Response Elements; Retinoic acid signaling; Signal Transduction; Tretinoin - metabolism; Tretinoin - pharmacology; Two-Hybrid System Techniques; WTIP; RAR; HARE-HTH; NR; Heart development; Asx; Epicardium; Retinoic acid signaling; WTIP; PHD; RA; PRC2; uH2A; ASXL2; ASXL; PR-DUB; ASXH; ATRA; H3K27me3
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2014.07.080

•ASXL2 directly interacts with the LIM-domain protein WTIP.•ASXL2 enhances retinoic acid-induced reporter transcription in HeLa cells.•WTIP represses RA signaling and blocks ASXL2’s activating effect.•LIM 2 and 3 of WTIP mediate both ASXL2-interaction and transcriptional repression.•ASXL2 and WTIP are expressed in mouse embryonic epicardial cells. The Asx-like (ASXL) family proteins are chromatin factors that play dual roles in transcriptional activation and repression. ASXL2 is highly expressed in the heart and is required for proper heart development and function. Here, we identify a novel ASXL2-binding partner, the LIM domain-containing protein WTIP. Genetic and biochemical assays show a direct interaction between ASXL2 and WTIP. In HeLa cells, ASXL2 enhances retinoic acid-dependent luciferase activity, while WTIP represses it. Furthermore, WTIP blocks ASXL2’s stimulatory effect on transcription. In addition, we found that ASXL2 and WTIP are expressed in mouse embryonic epicardial cells, a tissue that is regulated by retinoic acid signaling. Together, these results implicate ASXL2 and WTIP in regulation of retinoic acid signaling during heart development.