Jae W. Lee
PhD
Research Interests
Genetic and epigenetic regulation of the hypothalamus arcuate nucleus development
Education
- PhD, Texas A&M University, College Station
Research Summary
We are recruiting postdocs as well as undergraduate and graduate students.
Jae Lee has purified two important transcriptional coactivator complexes, ASC-1 complex, which links splicing to transcription, and ASC-2 complex (ASCOM, aka MLL3/4-complexes), which represents the first histone H3 lysine 4 methyltransferase (H3K4MT) complex identified in mammals (containing either the H3K4MT MLL3/KMT2C or its paralog MLL4/KMT2D). ASCOM belongs to a family of similar mammalian complexes, collectively named Set1-like complexes. In humans, mutations in MLL4 but not MLL3 are known to cause a developmental disorder named Kabuki syndrome. In a striking demonstration of a specificity of individual Set1-like complexes, Lee discovered that mutant mouse models for Mll4 (but NOT Mll3) also recapitulate many features of the Kabuki syndrome. More recently, Lee has begun pioneering the gene regulatory network responsible for embryonic development of hypothalamic arcuate neurons that control feeding, energy expenditure, reproduction and growth.
Selected Publications
- The histone demethylase Kdm6b regulates subtype diversification of mouse spinal motor neurons during development by Wenxian Wang, Hyeyoung Cho, Jae Lee, and Soo-Kyung Lee, Nature Communications, in press, 2022.
- Huisman C, Kim YA, Jeon S, Shin B, Choi J, Lim SJ, Youn SM, Park Y, K C M, Kim S, Lee SK, Lee S, Lee JW. The histone H3-lysine 4-methyltransferase Mll4 regulates the development of growth hormone-releasing hormone-producing neurons in the mouse hypothalamus. Nat Commun. 2021 Jan 11;12(1):256. doi: 10.1038/s41467-020-20511-7.
- Wang W, Cho H, Kim D, Park Y, Moon JH, Lim SJ, Yoon SM, McCane M, Aicher SA, Kim S, Emery B, Lee JW, Lee S, Park Y, Lee SK (2020) PRC2 Acts as a Critical Timer That Drives Oligodendrocyte Fate over Astrocyte Identity by Repressing the Notch Pathway. Cell Rep 32:108147. Paper is here.
- Huisman, C., Cho, H., Brock, O., Lim, S.J., Youn, S.M., Park, Y., Kim, S., Lee, S.-K., Delogu, A. and Lee, J.W. (2019) Single cell transcriptome analysis of developing arcuate nucleus neurons uncovers their key developmental regulators. Nature Commun., 10, 3696. doi: 10.1038/s41467-019-11667-y.
- Lee, B., Kim, J., An, T., Kim, S., Patel, E.M., Raber, J., Lee, S.K., Lee, S., & Lee, J.W. (2018). Dlx1/2 and Otp coordinate the production of hypothalamic GHRH- and AgRP-neurons. Nature Commun., 9, 2026. Doi: 10.1038/s41467-018-04377-4.
- Kim, D.H., Kim, J., Kwon, J.S., Sandhu, J., Tontonoz, P., Lee, S.K., Lee, S., and Lee, J.W. (2016). Critical roles of the histone methyltransferase MLL4/KMT2D in murine hepatic steatosis directed by ABL1 and PPARγ2. Cell Reports, 17, 1671-1682.
- Kim, D.H. and Lee, J.W.(2011). The tumor suppressor p53 regulates bile acid homeostasis via small heterodimer partner. Proc. Natl. Acad. Sci. USA108, 12266-12270.
- Lee, J., Kim, D., Lee, S., Yang, Q., Lee, D.K., Lee, S.K., Roeder, R.G., & Lee, J.W. (2009). A tumor suppressive coactivator complex of p53 containing ASC-2 and histone H3-lysine-4 methyltransferase MLL3 or its paralogue MLL4. Proceedings of the National Academy of Sciences, 106, 18513-8518.
- Lee, J., Saha, P.K., Yang, Q., Lee, S., Park, J.Y., Suh, Y.S., Lee, S.K., Chan, L., Roeder, R.G., Lee, J.W. (2008). Targeted inactivation of MLL3 histone H3–Lys-4 methyltransferase activity in the mouse reveals vital roles for MLL3 in adipogenesis. Proceedings of the National Academy of Sciences, 49, 19229-19234.
- Lee, S., Lee, D., Dou, Y., Lee, J., Lee, B., Kwak, E., Kong, Y., Lee, S.K., Roeder, R.G., & Lee, J.W. (2006). Coactivator as a target gene specificity determinant for histone H3 lysine 4 methyltransferases. Proceedings of the National Academy of Sciences, 103, 15392-15397.