Long noncoding RNAs in epigenetic programming – The general interest of the Sun laboratory is to understand how a living cell controls its genetic and epigenetic composition. The main focus of our research involves the functional roles of long noncoding RNAs (lncRNAs) in epigenetic programming. Increasing evidence from large-scale transcriptome sequencing projects suggests a high abundance of lncRNAs present in human genome and potentially significant roles of lncRNAs in various aspects of biological processes. The research projects in our lab will address the following three questions: 1) What are molecular features required for lncRNA function? 2) What are the mechanisms for lncRNA regulation? 3) How have lncRNA functions evolved?
1. Currently, we use mammalian X chromosome inactivation (XCI) as a model to investigate the specificity of lncRNAs in dosage sensing. As unique machinery achieving whole-chromosome gene silencing, XCI is predominately controlled by lncRNAs that capable of sensing chromosome numbers and tuning gene expression. Using embryonic stem cells and transgenic mice, we are interested in identifying and characterizing lncRNAs for X chromosome counting. Our research aims to capture essential features (i.e. RNA sequence and structure motifs, temporal and tissue-specific regulation, etc.) that confer lncRNA function in gene dosage control.
2. With the rapid expansion of prediction and identification of lncRNAs in stem cell reprogramming and cancer, our lab is also interested to identify disease-associated lncRNAs that involve chromosomal aneuploidies or copy-number variations (CNVs). Our research findings will contribute to a comprehensive understanding of noncoding RNA regulation and will help provide new avenues for disease therapy.
3. As “nothing in biology makes sense except in the light of evolution” (Dobzhansky 1973), we seek to address the origin and evolution of lncRNA functions using comparative sequence and functional analyses with molecular genetic tools in mouse ES cells.
- I. Naciri, B. Lin, C.-H. Webb, S. Jiang, S. Carmona, W. Liu, A. Mortazavi, S. Sun. Linking Chromosomal Silencing with Xist Expression from Autosomal Integrated Transgenes. Frontiers in Cell and Developmental Biology (2021)
- L. Abdelhamid, X. Cabana-Puig, B. Swartwout, J. Lee, S. Li, S. Sun, Y. Li, A. C. Ross, T. E. Cecere, T. LeRoith, S. R. Werre, H. Wang, C. M. Reilly, X. M. Luo. Retinoic Acid Exerts Disease Stage-Dependent Effects on Pristane-Induced Lupus. Frontiers in Immunology 11: 408 (2020)
- H. Karner, C. Webb, S. Carmona, Y. Liu, B. Lin, M. Erhard, D. Chan, P. Baldi, R. C. Spitale, S. Sun. Functional conservation of lncRNA JPX despite sequence and structural divergence. Journal of Molecular Biology 432: 283-300 (2020) Featured Article & Cover.
- H. Xu, Z. Tong, Q. Ye, T. Sun, Z. Hong, L. Zhang, A. Bortnick, S. Cho, P. Beuzer, J. Axelrod, Q. Hu, M. Wang, S. M. Evans, C. Murre, L. F. Lu, S. Sun, K. D. Corbett, H. Cang. Molecular organization of mammalian meiotic chromosome axis revealed by expansion STORM microscopy. PNAS . (2019)
- S. Carmona, B. Lin, T. Chou, K. Arroyo, S. Sun. LncRNA Jpx induces Xist expression in mice using both trans and cis mechanisms. PLOS Genetics 14(5): e1007378 (2018).
- L. Yu, S. Sun, M. Wood, T. W. Bredy, R. C. Spitale, P. Baldi. MotifMap-RNA: A comprehensive map of RBP binding sites. Bioinformatics 33: 2029-2031 (2017).
- J. F. Shaffer and S. Sun. Anencephaly in Yakima: Lots of questions, no answers. National Center for Case Study Teaching in Science. National Center for Case Study Teaching in Science (2017).
- C. Li, T. Hong, C.-H. Webb, H. Karner, S. Sun*, Q. Nie*. A self-enhanced transport mechanism through long noncoding RNAs for X chromosome inactivation. Scientific Reports 6: 31517 (2016). (* Co-corresponding author)
- S. Sun, B. Payer, S. Namekawa, J. Y. An, W. Press, J. Catelan-Dibene, H. Sunwoo, and J. T. Lee. Xist imprinting is promoted by the hemizygous (unpaired) state in the male germline. PNAS 112:14415-22 (2015)
- X. Liao, S. Li, R. E. Settlage, S. Sun, J. Ren, A. M. Reihl, H. Zhang, S. V. Karyala, C. M. Reilly, S. A. Ahmed, X. M. Luo. Cutting Edge: Plasmacytoid Dendritic Cells in Late-Stage Lupus Mice Defective in Producing IFNα. Journal of Immunology 195:4578-82 (2015)
- S. Sun, B. C. Del Rosario, A. Szanto, Y. Ogawa, Y. Jeon, and J. T. Lee. Jpx RNA activates Xist by evicting CTCF. Cell 153: 1537-1551 (2013)
- D. Tian, S. Sun, and J. T. Lee. The long noncoding RNA, Jpx, is a molecular switch for X chromosome inactivation. Cell 143: 390-413 (2010)
- S. Sun*, Y. Fukue*, L. Nolen, R. I. Sadreyev, and J. T. Lee. Characterization of Xpr (Xpct) reveals instability but no effects on X-chromosome pairing or Xist expression. Transcription 1: 46-56 (2010) Cover Article (* Equal contribution.)
- T. W. Cline, M. Dorsett*, S. Sun*, M. M. Harrison, J. Dines, L. Sefton, and L. Megna. Evolution of the Drosophila feminizing switch gene Sex-lethal. Genetics 186: 1321-1336 (2010) (* Equal contribution.)
- S. Sun, and T.W. Cline. Effects of Wolbachia infection and ovarian tumor mutations on Sex-lethal germline functioning in Drosophila. Genetics 181: 1291-1301 (2009)
- S. Sun, C.-T. Ting, and C.-I Wu. The normal function of a speciation gene, Odysseus, and its hybrid male sterility effect. Science 305: 81-83 (2004)
- C.-T. Ting, S. C. Tsaur, S. Sun, W. Browne, N. H. Patel, and C.-I Wu. Gene duplication and speciation in Drosophila – Evidence from the Odysseus locus. PNAS 101: 12232-12235 (2004)