Di  Zhang  lab 

Research interest:

Di Zhang's lab is dedicated to investigate new regulatory pathways of cellular metabolism regulating chromatin activity and how their abnormalities lead to human diseases such as tumors, autoimmune diseases and aging. Their major contributions in this area include: 

Identification of a new histone modification driven by L-lactate, lysine lactylation; Identification of a new histone modification driven by ketone body, lysine β-hydroxybutyrylation. These metabolite-driven histone marks link gene transcription and cellular metabolism to adapt the cellular response to environmental changes.


(*Co-first author, # Corresponding author)

1. Ren, H., Zhang, D.# (2024) Lactylation constrains OXPHOS under hypoxia. Cell Res.


2. Moreno-Yruela, C., Zhang, D*., Wei, W., Bæk, M., Liu, W., Gao, J., Danková, D., Nielsen, A. L., Bolding, J. E., Yang, L., Jameson, S. T., Wong, J., Olsen, C. A., & Zhao, Y. (2022). Class I histone deacetylases (HDAC1-3) are histone lysine delactylases. Sci Adv, 8(3), eabi6696.


3. 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. 

4. 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.  

5. 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. 

6. 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. 

7. 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. 

8. 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. 

9. 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. 

10. 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; From wiki


Nature 574,575-580 (2019)pagvolu574page