Zhenhua Yang*, Jonathan Augustin*, Chenbei Chang, Jing Hu, Kushani Shah, Chia-Wei Chang, Tim Townes, and Hao Jiang. The DPY30 subunit in SET1/MLL complexes regulates the proliferation and differentiation of hematopoietic progenitor cells. Blood. Accepted. * Equal contribution.
Hao Jiang, Abhijit Shukla, Xiaoling Wang, Wei-yi Chen, Bradley E. Bernstein, and Robert G. Roeder. Role for Dpy-30 in ES cell-fate specification by regulation of H3K4 methylation within bivalent domains. Cell 144:513-525, 2011. (PMID: 21335234)
Hao Jiang*, Xiangdong Lu*, Miho Shimada, Yali Dou, Zhanyun Tang, and Robert G. Roeder. A direct role for MLL2 complex-mediated H3K4 methylation in transcription and its regulation by the associated AKAP95. Nature Structural & Molecular Biology. 20:1156-1163, 2013. * Equal contribution. (PMID: 23995757)
Areas of Focus: My lab studies roles of histone modifications, with a particular focus on histone H3K4 methylation, in the regulation of gene expression in stem cell fate determination.
The central properties of the embryonic stem cells lie in their continuous self-renewal while maintaining the potential to differentiate into all types of cells in the organism. It has recently been demonstrated that various types of differentiated cells can be reverted to the pluripotent state or can be converted to one another. Controlling the stability and plasticity of cell identity is obviously crucial for animal development and physiology, and is also pivotal for regenerative medicine. With a few exceptions, all cells in an organism share the same genome, but they do have different epigenomes and gene expression patterns.Therefore, at the heart of the cell identity control is the control of gene expression. Epigenetic mechanisms including the covalent chemical modifications on histones are increasingly recognized as a fundamental and prevalent means to regulate gene expression. In a simplistic view, histone H3K4 methylation is
generally associated with gene activation, while H3K27 methylation with gene repression. However, it is still difficult today to give definitive answers to some simple yet fundamental questions including: Is H3K4 methyl mark functionally critical for transcription? If yes, then to what extent does it impact on animal physiology?
My postdoctoral work has shown that DPY30, a conserved common subunit of MLL family complexes (the major H3K4 methyltransferases in mammals), plays an essential functional role in priming the developmental genes for efficient induction during ES cell fate specification (Jiang et al, Cell 2011). My recent work has also identified AKAP95 as a novel factor associated with the DPY30/MLL complexes, and demonstrated its activity in modulating histone modification by the complexes, in co-activating chromatin transcription, and in mediating efficient gene induction upon ES cell fate transition (Jiang et al, Nat Struct Mol Biol 2013).
Current and future research in the lab continues to focus on the epigenetic regulation of gene expression critically involved in stem cell fate determination. We employ a combination of biochemical, genetic and genomic approaches to investigate the physiological roles of the H3K4 methyltransferases as well as their associated factors in gene regulation involved in the maintenance and differentiation of stem cells in animal development.