BRPF1 bridges H3K4me3 and H3K23ac in human embryonic stem cells and is essential to pluripotency

Cong Zhang; Huaisong Lin; Yanqi Zhang; Qi Xing; Jingyuan Zhang; Di Zhang; Yancai Liu; Qianyu Chen; Tiancheng Zhou; Junwei Wang; Yongli Shan; Guangjin Pan

doi:10.1016/j.isci.2023.105939

BRPF1 bridges H3K4me3 and H3K23ac in human embryonic stem cells and is essential to pluripotency

iScience. 2023 Jan 5;26(2):105939. doi: 10.1016/j.isci.2023.105939. eCollection 2023 Feb 17.

Authors

Cong Zhang^{1

2

3

4}, Huaisong Lin^{1

3

4}, Yanqi Zhang^{1

2

3

4}, Qi Xing^{1

2

3

4}, Jingyuan Zhang^{1

2

3

4}, Di Zhang^{1

2

3

4}, Yancai Liu^{1

5}, Qianyu Chen^{1

3

4}, Tiancheng Zhou^{1

3

4}, Junwei Wang^{1

3

4}, Yongli Shan^{1

3

4}, Guangjin Pan^{1

2

3

4

6}

Affiliations

¹ CAS Key Laboratory of Regenerative Biology, Centre for Regenerative Medicine and Health, Hong Kong Institute of Science and Innovation, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China.
² University of Chinese Academy of Sciences, Beijing 100049, China.
³ CAS Key Laboratory of Regenerative Biology, Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, Center for Cell Lineage and Development, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China.
⁴ Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China.
⁵ Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui 230027, China.
⁶ Key Lab for Rare & Uncommon Diseases of Shandong Province, Biomedical Sciences College & Shandong Medicinal Biotechnology Centre, Shandong First Medical University & Shandong Academy of Medical Sciences, Ji'nan, Shandong 250117, China.

Abstract

Post-translational modifications (PTMs) on histones play essential roles in cell fate decisions during development. However, how these PTMs are recognized and coordinated remains to be fully illuminated. Here, we show that BRPF1, a multi-histone binding module protein, is essential for pluripotency in human embryonic stem cells (ESCs). BRPF1, H3K4me3, and H3K23ac substantially co-occupy the open chromatin and stemness genes in hESCs. BRPF1 deletion impairs H3K23ac in hESCs and leads to closed chromatin accessibility on stemness genes and hESC differentiation as well. Deletion of the N terminal or PHD-zinc knuckle-PHD (PZP) module in BRPF1 completely impairs its functions in hESCs while PWWP module deletion partially impacts the function. In sum, we reveal BRPF1, the multi-histone binding module protein that bridges the crosstalk between different histone modifications in hESCs to maintain pluripotency.

Keywords: Cell biology; Genetics; Molecular genetics; Stem cells research.