Genetic and epigenetic regulation of the hypothalamus arcuate nucleus development
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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.
Research Project | Sponsor | PI | Period | Amount |
Transcription factors governing the development of GHRH-neurons | NINDS/NIH | Jae Lee | 8/1/2021-7/31/2025 | $547873 a year |
Construction and characterization of humanized FoxG1 mouse models | FoxG1 Research Foundation | Jae Lee | July 1, 2020-June 30, 2023 | $400,000 a year |
Molecular dissection of forebrain developmental deficits caused by mutations in human FoxG1 syndrome | FoxG1 Research Foundation | Soo Lee | July 1, 2020-June 30, 2023 | $200,000 a year |
Transcriptional regulators of motor columnar specification | NINDS/NIH | Soo Lee | 04/01/2019 – 03/31/2024 | $2,494,667 |
FoxG1-directed Gene network in forebrain development and FoxG1 syndrome | NINDS/NIH | Soo Lee | 06/01/2017 – 04/30/2022 | $2,412,778 |
Roles Of Mll4-Complex In Development Of Hypothalamic Arcuate Neurons | NIDDK/NIH | Jae Lee | July 1, 2020-June 30, 2021 | $81,001 |
Transcription Factors Governing The Development Of Ghrh-Neurons | NINDS/NIH | Jae Lee | July 1, 2020-June 30, 2021 | $558,250 |