Research Interest
Epigenetic mechanisms including chromatin modifications, play essential gene regulatory roles in cell-type identity as well as in human diseases. It is becoming increasingly clear that there is a close link between nutrient state, energy metabolism and epigenetics. The classic examples are histone methylation and acetylation, which are derived from cellular metabolites S-adenosyl methionine and acetyl-CoA, respectively. Nevertheless, we know very little about whether there exist additional epigenetic pathways that use other metabolites as cofactors, and how cellular metabolites regulate gene function in general are largely unclear.
Dr. Zhang first time identified histone lactylation and beta-hydroxybutyrylation, which are derived from lactate and ketone body accordingly. Dr. Zhang’s group are now interested in the molecular mechanisms mediating the crosstalk between metabolism and epigenetics. Using biochemistry, genetic, and multi-omics technology, we are focused to identify and study new types of chromatin modifications, new functions of metabolic enzymes, and how these mechanisms function in normal development, aging, and in human diseases including cancer, autoimmunity, etc.
Publication
*Equal contribution.
1. Huang H, Zhang D*, Weng Y, Delaney K, Tang Z, Yan C, Qi S, Peng C, Cole PA, Roeder RG, Zhao Y (2021). The regulatory enzymes and protein substrates for the lysine β-hydroxybutyrylation pathway. Sci Adv. 7(9): eabe2771.
2. Zhang D*, Tang Z*, Huang H, Zhou G, Cui C, Weng Y, Liu W, Kim S, Lee S, Perez-Neut M, Czyz D, Hu R, Ye Z, He M, Zheng YG, Shuman H, Ding J, Dai L, Ren B, Robert RG, Becker L, Zhao Y. (2019) Metabolic regulation of gene expression by histone lactylation. Nature. 574: 575-580.
Highlighted by
Nature news & views: https://www.nature.com/articles/d41586-019-03122-1
Science Signaling Editor’s choice: https://stke.sciencemag.org/content/12/606/eaba0502.full
Nature Immunology Research Highlight: https://www.nature.com/articles/s41590-019-0551-6
Trends in Biochemical Sciences Spotlight:https://www.sciencedirect.com/science/article/abs/pii/S0968000419302658
Immunity Preview: https://www.sciencedirect.com/science/article/pii/S1074761319304893
Nature reviews immunology Year in Review: MACROPHAGES IN 2019: https://www.nature.com/articles/s41577-019-0260-2
Nature reviews immunology Year in Review: INFLAMMATION IN 2019: https://www.nature.com/articles/s41577-019-0259-8
Cited by
Nature reviews Cancer, Nature reviews immunology, Nature reviews Genetics, Nature reviews Microbiology, Nature reviews Endocrinology, Trends in biochemical Sciences, Trends in Cell Biology, Trends in Immunology
3. Huang H, Zhang D, Wang Y, Perez-Neut M, Han Z, Zheng YG, Hao Q, Zhao Y. (2018). Lysine benzoylation is a histone mark regulated by SIRT2. Nat Commun. 9(1):3374.
4. Sabari BR*, Zhang D*, Allis CD, Zhao Y. (2017). Metabolic Regulation of Gene Expression through Differential Histone Acylation. Nat Rev Mol Cell Biol. 18(2):90-101.
5. Xie Z*, Zhang D*, Chung D*, Tang Z, Huang H, Dai L, Qi S, Li J, Colak G, Chen Y, Xia C, Peng C, Ruan H, Kirkey M, Wang D, Jensen LM, Kwon OK, Lee S, Pletcher SD, Tan M, Lombard DB, White KP, Zhao H, Li J, Roeder RG, Yang X, Zhao Y. (2016). Metabolic Regulation of Gene Expression by Histone Lysine beta-hydroxybutyrylation. Mol Cell. 62 (2):194-206.
6. Goudarzi A*, Zhang D*, Huang H, Barral S, Kwon OK, Qi S, Tang Z, Buchou T, Vitte AL, He T, Cheng Z, Montellier E, Gaucher J, Curtet S, Debernardi A, Charbonnier G, Puthier D, Petosa C, Panne D, Rousseaux S, Roeder RG, Zhao Y‡, Khochbin S‡. (2016). Dynamic Competing Histone H4 K5K8 Acetylation and Butyrylation Are Hallmarks of Highly Active Gene Promoters. Mol Cell. 62(2): 169-80.
7. Zhang Y*, Zhang D*, Liang J, Yi X, Gui B, Yu W, Sun L, Yang X, Han X, Chen Z, Liu S, Si W, Yan R, Wang Y, Shang Y‡. (2016). Nucleation of DNA Repair Factors by FOXA1 Links DNA Demethylation to Transcriptional Pioneering. Nat Genet. 48 (9):1003-13.
8. Li L, Shi L, Yang S, Yan R, Zhang D, Yang J, He L, Li W, Yi X, Sun L, Liang J, Cheng Z, Shi L, Yu W, Shang Y‡. (2016). SIRT7 Is a Histone Desuccinylase that Functionally Links to Chromatin Compaction and Genome Stability. Nat Commun. 7:12235.
Metabolism
https://en.wikipedia.org/wiki/Metabolic_pathway; From wiki
Lactylation
Nature 574，575-580 (2019)