Guang Yang

All Publications

• Defining a TFAP2C-centered transcription factor network during murine peri-implantation. Developmental cell Gao, R., Yang, G., Wang, M., Xiao, J., Yi, S., Huang, Y., Guo, Z., Kang, Y., Fu, Q., Wang, M., Xu, B., Shen, S., Zhu, Q., Liu, M., Wang, L., Cui, X., Yi, S., Kou, X., Zhao, Y., Gu, L., Wang, H., Gao, S., Jiang, C., Chen, J. 2024; 59 (9): 1146-1158.e6

  Abstract

  Transcription factors (TFs) play important roles in early embryonic development, but factors regulating TF action, relationships in signaling cascade, genome-wide localizations, and impacts on cell fate transitions during this process have not been clearly elucidated. In this study, we used uliCUT&RUN-seq to delineate a TFAP2C-centered regulatory network, showing that it involves promoter-enhancer interactions and regulates TEAD4 and KLF5 function to mediate cell polarization. Notably, we found that maternal retinoic acid metabolism regulates TFAP2C expression and function by inducing the active demethylation of SINEs, indicating that the RARG-TFAP2C-TEAD4/KLF5 axis connects the maternal-to-zygotic transition to polarization. Moreover, we found that both genomic imprinting and SNP-transferred genetic information can influence TF positioning to regulate parental gene expressions in a sophisticated manner. In summary, we propose a ternary model of TF regulation in murine embryonic development with TFAP2C as the core element and metabolic, epigenetic, and genetic information as nodes connecting the pathways.

  View details for DOI 10.1016/j.devcel.2024.03.015

  View details for PubMedID 38574734

• Dux-Mediated Corrections of Aberrant H3K9ac during 2-Cell Genome Activation Optimize Efficiency of Somatic Cell Nuclear Transfer. Cell stem cell Yang, G., Zhang, L., Liu, W., Qiao, Z., Shen, S., Zhu, Q., Gao, R., Wang, M., Wang, M., Li, C., Liu, M., Sun, J., Wang, L., Liu, W., Cui, X., Zhao, K., Zang, R., Chen, M., Liang, Z., Wang, L., Kou, X., Zhao, Y., Wang, H., Wang, Y., Gao, S., Chen, J., Jiang, C. 2021; 28 (1): 150-163.e5

  Abstract

  Differentiated somatic cells can be reprogrammed to totipotent embryos through somatic cell nuclear transfer (SCNT) with low efficiency. The histone deacetylase inhibitor trichostatin A (TSA) has been found to improve SCNT efficiency, but the underlying mechanism remains undetermined. Here, we examined genome-wide H3K9ac during SCNT embryo development and found that aberrant H3K9ac regions resulted in reduced 2-cell genome activation. TSA treatment largely corrects aberrant acetylation in SCNT embryos with an efficiency that is dictated by the native epigenetic environment. We further identified that the overexpression of Dux greatly improves SCNT efficiency by correcting the aberrant H3K9ac signal at its target sites, ensuring appropriate 2-cell genome activation. Intriguingly, the improvement in development mediated by TSA and Kdm4b is impeded by Dux knockout in SCNT embryos. Together, our study reveals that reprogramming of H3K9ac is important for optimal SCNT efficiency and identifies Dux as a crucial transcription factor in this process.

  View details for DOI 10.1016/j.stem.2020.09.006

  View details for PubMedID 33049217

• Chromatin landscape instructs precise transcription factor regulome during embryonic lineage specification. Cell reports Wang, L., Yi, S., Cui, X., Guo, Z., Wang, M., Kou, X., Zhao, Y., Wang, H., Jiang, C., Gao, S., Yang, G., Chen, J., Gao, R. 2024; 43 (5): 114136

  Abstract

  Embryos, originating from fertilized eggs, undergo continuous cell division and differentiation, accompanied by dramatic changes in transcription, translation, and metabolism. Chromatin regulators, including transcription factors (TFs), play indispensable roles in regulating these processes. Recently, the trophoblast regulator TFAP2C was identified as crucial in initiating early cell fate decisions. However, Tfap2c transcripts persist in both the inner cell mass and trophectoderm of blastocysts, prompting inquiry into Tfap2c's function in post-lineage establishment. In this study, we delineate the dynamics of TFAP2C during the mouse peri-implantation stage and elucidate its collaboration with the key lineage regulators CDX2 and NANOG. Importantly, we propose that de novo formation of H3K9me3 in the extraembryonic ectoderm during implantation antagonizes TFAP2C binding to crucial developmental genes, thereby maintaining its lineage identity. Together, these results highlight the plasticity of the chromatin environment in designating the genomic binding of highly adaptable lineage-specific TFs and regulating embryonic cell fates.

  View details for DOI 10.1016/j.celrep.2024.114136

  View details for PubMedID 38643480