Species-specific rewiring of definitive endoderm developmental gene activation via endogenous retroviruses through TET1-mediated demethylation

Wu，Fang1,2; Liufu，Zhongqi3; Liu，Yujian1; Guo，Lin1; Wu，Jian1; Cao，Shangtao4; Qin，Yue5; Guo，Ning1; Fu，Yunyun1; Liu，He6; Li，Qiuhong1; Shu，Xiaodong1; Pei，Duanqing1,5; Hutchins，Andrew P.7; Chen，Jiekai1,2; He，Jiangping4

2022-12-13

10.1016/j.celrep.2022.111791

Cell Reports   Impact Factor & Quartile

2211-1247

Transposable elements (TEs) are the major sources of lineage-specific genomic innovation and comprise nearly half of the human genome, but most of their functions remain unclear. Here, we identify that a series of endogenous retroviruses (ERVs), a TE subclass, regulate the transcriptome at the definitive endoderm stage with in vitro differentiation model from human embryonic stem cell. Notably, these ERVs perform as enhancers containing binding sites for critical transcription factors for endoderm lineage specification. Genome-wide methylation analysis shows most of these ERVs are derepressed by TET1-mediated DNA demethylation. LTR6B, a representative definitive endoderm activating ERV, contains binding sites for FOXA2 and GATA4 and governs the primate-specific expression of its neighboring developmental genes such as ERBB4 in definitive endoderm. Together, our study proposes evidence that recently evolved ERVs represent potent de novo developmental regulatory elements, which, in turn, fine-tune species-specific transcriptomes during endoderm and embryonic development.

CP: Developmental biology CP: Molecular biology DNA methylation endogenous retroviruses gene regulation human development TET1 transcriptional networks transposable elements

SCI

English

Others

National Key Research and Development Program of China[2019YFA0110200];Science and Technology Planning Project of Guangdong Province[2020B1212060052];National Key Research and Development Program of China[2020YFA0112403];National Key Research and Development Program of China[2021YFA1102200];National Natural Science Foundation of China[32200461];Chinese Academy of Sciences[ZDBS-LY-SM007];

WOS:000901764900002

2-s2.0-85143866159

Scopus

1.Center for Cell Lineage and Development,Guangzhou Institutes of Biomedicine and Health,Chinese Academy of Sciences,Guangzhou,510530,China
2.University of the Chinese Academy of Sciences,Beijing,100049,China
3.Key Laboratory of Biological Targeting Diagnosis,Therapy and Rehabilitation of Guangdong Higher Education Institutes,The Fifth Affiliated Hospital of Guangzhou Medical University,Guangzhou,510799,China
4.Guangzhou Laboratory,Bio-island,Guangzhou,510320,China
5.School of Life Sciences,Westlake University,Hangzhou,China
6.Center for Cell Lineage and Atlas (CCLA),Bioland Laboratory (Guangzhou Regenerative Medicine and Health Guangdong Laboratory),Guangzhou,510320,China
7.Shenzhen Key Laboratory of Gene Regulation and Systems Biology,Department of Biology,School of Life Sciences,Southern University of Science and Technology,Shenzhen,518055,China

Wu，Fang,Liufu，Zhongqi,Liu，Yujian,et al. Species-specific rewiring of definitive endoderm developmental gene activation via endogenous retroviruses through TET1-mediated demethylation[J]. Cell Reports,2022,41(11).

Wu，Fang.,Liufu，Zhongqi.,Liu，Yujian.,Guo，Lin.,Wu，Jian.,...&He，Jiangping.(2022).Species-specific rewiring of definitive endoderm developmental gene activation via endogenous retroviruses through TET1-mediated demethylation.Cell Reports,41(11).

Wu，Fang,et al."Species-specific rewiring of definitive endoderm developmental gene activation via endogenous retroviruses through TET1-mediated demethylation".Cell Reports 41.11(2022).