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Regulation of human trophoblast gene expression by endogenous retroviruses [ChIP-seq]

ABSTRACT: Regulation of human trophoblast gene expression by endogenous retroviruses [ChIP-seq]

PROVIDER: PRJNA826509 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR18745741_1.fastq.gz	Fastqsanger.gz
	SRR18745741_2.fastq.gz	Fastqsanger.gz
	SRR18745742_1.fastq.gz	Fastqsanger.gz
	SRR18745742_2.fastq.gz	Fastqsanger.gz
	SRR18745743_1.fastq.gz	Fastqsanger.gz

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Regulation of human trophoblast gene expression by endogenous retroviruses

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Regulation of human trophoblast gene expression by endogenous retroviruses [ChIP-seq]

Project description:The placenta is a fast-evolving organ that displays large morphological and histological differences across eutherians, but the genetic changes driving placental evolution have not been fully elucidated. Transposable elements, through their capacity to quickly generate genetic variation and affect host gene regulation, may have helped to define species-specific trophoblast gene expression programmes. Here were assessed the contribution of transposable elements to human trophoblast gene expression by acting as enhancers or promoters. Using epigenomic data from primary trophoblast and human stem cell lines, we identified multiple endogenous retrovirus families with regulatory potential that lie close to genes with preferential trophoblast expression. These largely primate-specific elements are associated with inter-species gene expression differences, and are bound by transcription factors with key roles in placental development. Using genetic editing we demonstrated that several elements act as expression enhancers of important placental genes, such as CSF1R and PSG5. We also identified an LTR10A element that regulates ENG expression, affecting trophoblast migration and secretion of soluble ENG, with potential implications for preeclampsia. Our data show that transposons have made important contributions to human trophoblast gene regulation, and suggest that their activity may affect pregnancy outcomes.

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Endogenous retrovirus MER50-derived enhancers confer the transcriptional regulation of human trophoblast syncytialization [ChIP-Seq]

Project description:Multinucleated syncytiotrophoblasts (STBs), which are in direct contact with maternal blood, constitute the maternal-fetal interface critical for nutrient allocation, hormone production and immunological modulation during pregnancy. However, the genetic and epigenetic regulatory mechanisms governing trophoblast syncytialization remain largely elusive. We delineate that endogenous retroviruses (ERVs), which have been exapted as regulatory sequences for specific functional adaptations in placenta, profoundly rewire transcriptional program of trophoblast syncytialization. Here, we first determined dynamic bivalent ERV-derived enhancers with dual occupancy of H3K9me3 and H3K27ac in human trophoblast stem cells (hTSCs), which emerge as cell specific regulators of gene expression with markedly resolved H3K9me3 during differentiation towards STBs. Of note, bivalent enhancers derived from the Simiiformes-specific MER50 transposons were linked to a cluster of STB-specific genes. Importantly, depletions of MER50 elements adjacent to several STB genes, including MFSD2A, TNFAIP2 and RAI14, significantly attenuated their expression concomitant to dysregulated syncytium formation. Together, we propose that ERV-derived enhancers, MER50 specifically, fine-tune the transcriptional program accounting for human trophoblast syncytialization, which sheds light on novel epigenetic regulatory mechanisms underlying placental development.

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