Chromatin landscape instructs precise transcription factor regulome during embryonic lineage specification

Liping Wang; Shanru Yi; Xinyu Cui; Zhenxiang Guo; Mengting Wang; Xiaochen Kou; Yanhong Zhao; Hong Wang; Cizhong Jiang; Shaorong Gao; Guang Yang; Jiayu Chen; Rui Gao

doi:10.1016/j.celrep.2024.114136

Chromatin landscape instructs precise transcription factor regulome during embryonic lineage specification

Cell Rep. 2024 Apr 20;43(5):114136. doi: 10.1016/j.celrep.2024.114136. Online ahead of print.

Authors

Liping Wang¹, Shanru Yi², Xinyu Cui³, Zhenxiang Guo⁴, Mengting Wang⁴, Xiaochen Kou⁴, Yanhong Zhao⁴, Hong Wang⁴, Cizhong Jiang⁵, Shaorong Gao⁶, Guang Yang⁷, Jiayu Chen⁸, Rui Gao⁹

Affiliations

¹ Shanghai Tenth People's Hospital, School of Life Sciences and Technology, Tongji University, Shanghai 200072, China; Frontier Science Center for Stem Cell Research, Tongji University, Shanghai 200092, China.
² Shanghai Tenth People's Hospital, School of Life Sciences and Technology, Tongji University, Shanghai 200072, China; Clinical and Translational Research Center of Shanghai First Maternity and Infant Hospital, Shanghai Key Laboratory of Signaling and Disease Research, School of Life Sciences and Technology, Tongji University, Shanghai 200092, China; Frontier Science Center for Stem Cell Research, Tongji University, Shanghai 200092, China.
³ Shanghai Tenth People's Hospital, School of Life Sciences and Technology, Tongji University, Shanghai 200072, China; Key Laboratory of Spine and Spinal Cord Injury Repair and Regeneration of the Ministry of Education, Orthopaedic Department of Tongji Hospital, School of Life Sciences and Technology, Tongji University, Shanghai 200065, China; Frontier Science Center for Stem Cell Research, Tongji University, Shanghai 200092, China.
⁴ Clinical and Translational Research Center of Shanghai First Maternity and Infant Hospital, Shanghai Key Laboratory of Signaling and Disease Research, School of Life Sciences and Technology, Tongji University, Shanghai 200092, China; Frontier Science Center for Stem Cell Research, Tongji University, Shanghai 200092, China.
⁵ Key Laboratory of Spine and Spinal Cord Injury Repair and Regeneration of the Ministry of Education, Orthopaedic Department of Tongji Hospital, School of Life Sciences and Technology, Tongji University, Shanghai 200065, China; Frontier Science Center for Stem Cell Research, Tongji University, Shanghai 200092, China.
⁶ Clinical and Translational Research Center of Shanghai First Maternity and Infant Hospital, Shanghai Key Laboratory of Signaling and Disease Research, School of Life Sciences and Technology, Tongji University, Shanghai 200092, China; Frontier Science Center for Stem Cell Research, Tongji University, Shanghai 200092, China; Shanghai Institute of Stem Cell Research and Clinical Translation, Shanghai East Hospital, Tongji University, Shanghai 200120, China. Electronic address: gaoshaorong@tongji.edu.cn.
⁷ Shanghai Tenth People's Hospital, School of Life Sciences and Technology, Tongji University, Shanghai 200072, China; Frontier Science Center for Stem Cell Research, Tongji University, Shanghai 200092, China. Electronic address: gyang@tongji.edu.cn.
⁸ Clinical and Translational Research Center of Shanghai First Maternity and Infant Hospital, Shanghai Key Laboratory of Signaling and Disease Research, School of Life Sciences and Technology, Tongji University, Shanghai 200092, China; Frontier Science Center for Stem Cell Research, Tongji University, Shanghai 200092, China. Electronic address: chenjiayu@tongji.edu.cn.
⁹ Clinical and Translational Research Center of Shanghai First Maternity and Infant Hospital, Shanghai Key Laboratory of Signaling and Disease Research, School of Life Sciences and Technology, Tongji University, Shanghai 200092, China; Frontier Science Center for Stem Cell Research, Tongji University, Shanghai 200092, China. Electronic address: gaorui@tongji.edu.cn.

PMID: 38643480
DOI: 10.1016/j.celrep.2024.114136

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.

Keywords: CP: Molecular biology; CP: Stem cell research; CUT&RUN; chromatin landscape; embryo development; heterochromatin; lineage specification; peri-implantation; super bivalency; transcription factor.