Zfp281 Shapes the Transcriptome of Trophoblast Stem Cells and Is Essential for Placental Development

Ishiuchi, Takashi; Ohishi, Hiroaki; Sato, Tetsuya; Kamimura, Satoshi; Yorino, Masayoshi; Abe, Shusaku; Suzuki, Atsushi; Wakayama, Teruhiko; Suyama, Mikita; Sasaki, Hidetada

doi:10.1016/j.celrep.2019.04.028

Cited by 33 publications

(37 citation statements)

References 64 publications

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“…Surprisingly, Zfp281 occupancy in WT 2i and WT 32 h cells was as highly correlated (Pearson's correlation coefficient R = 0.81) as between replicates ( R = 0.84 and R = 0.85, respectively), with only few peaks exclusively detected in any of the two cell states (Figs E and EV3D). A lower correlation was observed between WT 32 h cells and published data for EpiSCs (Huang et al , ; R = 0.69) and trophoblast stem cells (TSCs; Ishiuchi et al , ; R = 0.55), but binding at peaks associated with cluster 1–6 genes was largely unchanged (Fig EV3E and F), suggesting stable chromatin association also during later pluripotency progression and in lineage‐unrelated TSCs. To determine whether Zfp281 binds to CREs, we profiled histone H3 lysine 27 acetylation (H3K27ac), a chromatin mark associated with active promoters and enhancers.…”

Section: Resultsmentioning

confidence: 52%

“… AmRNA log 2 FC relative to WT 2i cells of selected core, naïve, and primed pluripotency markers in differentiating between WT and Zfp281 KO cells at indicated time points. BTop 5 enriched GO terms in clusters 1–6. CSequence logo from the de novo identified binding motif in 82.4% of 23,756 Zfp281 peaks. DScatter plot comparing log 2 Zfp281 peak ChIP enrichment over matched inputs between replicates in WT 2i (top) and WT 32 h (bottom) cells. E, FScatter plot comparing log 2 Zfp281 ChIP enrichment over matched inputs in WT 32 h cells and EpiSCs (Huang et al , ) (E) and TSCs (Ishiuchi et al , ) (F). Peaks were assigned to closest transcriptional start sites (TSSs) and colored according to association with gene clusters 1–6. GHeatmap of Zfp281, H3K27ac, histone H3K4 tri‐methylation (H3K4me3), H3K4 mono‐methylation (H3K4me1), and histone H3K27 tri‐methylation (H3K27me3) ChIP‐seq, DNase‐hypersensitive sites (DHS), and global run‐on sequencing (GRO‐seq) read densities across all proximal (± 2 kb of TSS) Zfp281 (top) and distal Zfp281 (bottom) peaks.…”

Section: Resultsmentioning

confidence: 99%

“…ChIP-seq data from this study, published datasets (Buecker et al, 2014;Huang et al, 2017;Ishiuchi et al, 2019), and DNase I hypersensitive site sequencing (DHS-seq) (Encode; accession number: ENCSR000CMW) reads were aligned to mouse GRCm38/mm10 genome using qAlign from the Bioconductor package QuasR with default parameters. Published H3K4me3, H3K27me3, and H3K9me2 ChIP-seq data (Kurimoto et al, 2015) were aligned using Bowtie (Langmead et al, 2009) (version 4.4.7) with parameter -C in colorspace.…”

Section: Chip-seq and Dhs-seq Analysismentioning

confidence: 99%

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Zfp281 orchestrates interconversion of pluripotent states by engaging Ehmt1 and Zic2

et al. 2019

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Developmental cell fate specification is a unidirectional process that can be reverted in response to injury or experimental reprogramming. Whether differentiation and de-differentiation trajectories intersect mechanistically is unclear. Here, we performed comparative screening in lineage-related mouse naïve embryonic stem cells (ESCs) and primed epiblast stem cells (EpiSCs), and identified the constitutively expressed zinc finger transcription factor (TF) Zfp281 as a bidirectional regulator of cell state interconversion. We showed that subtle chromatin binding changes in differentiated cells translate into activation of the histone H3 lysine 9 (H3K9) methyltransferase Ehmt1 and stabilization of the zinc finger TF Zic2 at enhancers and promoters. Genetic gain-of-function and loss-of-function experiments confirmed a critical role of Ehmt1 and Zic2 downstream of Zfp281 both in driving exit from the ESC state and in restricting reprogramming of EpiSCs. Our study reveals that cell type-invariant chromatin association of Zfp281 provides an interaction platform for remodeling the cisregulatory network underlying cellular plasticity.

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Section: Resultsmentioning

confidence: 52%

Section: Resultsmentioning

confidence: 99%

Section: Chip-seq and Dhs-seq Analysismentioning

confidence: 99%

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Zfp281 orchestrates interconversion of pluripotent states by engaging Ehmt1 and Zic2

et al. 2019

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“…Interestingly, these TFs are widely known to be involved in trophoblast differentiation. For example, Zfp281 (Krüppel-like zinc finger transcription factor), a zinc finger transcription factor, which shapes the transcriptome of trophoblast cells and regulates early placental development, has also been investigated in a recent article (Ishiuchi et al, 2019). Moreover, the other TFs were widely known to be important in placental development ( Supplementary Table S8).…”

Section: Transcription Factors That Bind Around Genomic Variations Sitesmentioning

confidence: 99%

Effect for Human Genomic Variation During the BMP4-Induced Conversion From Pluripotent Stem Cells to Trophoblast

Liu

et al. 2020

Front. Genet.

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The role of genomic variation in differentiation is currently not well understood. Here, the genomic variations were determined with the whole-genome sequencing for three pairs of pluripotent stem cell lines and their corresponding BMP4-induced trophoblast cell lines. We identified ∼3,500 single nucleotide variations and ∼4,500 indels by comparing the genome sequenced data between the stem cell lines and the matched BMP4induced trophoblast cell lines and annotated them by integrating the epigenomic and transcriptomic datasets. Relatively, introns enrich more variations. We found ∼45% (42 genes) of the differentially expressed genes in trophoblasts that associate genomic variations. Six variations, located at transcription factor binding sites where H3K4me3 and H3K27ac are enriched in both H1 and H1_BMP4, were identified. The epigenetic status around the genomic variations in H1 was similar to that in H1_BMP4. This means that the variation-associated gene's expression change can not be attributed to epigenetic alteration. The genes associated with the six variations were upregulated in differentiation. We inferred that during the differentiation, an increased in the expression level of the MEF2C gene is due to a genomic variation in chromosomes 5: 88179358 A > G, which is at a binding site of TFs KLF16, NR2C2, and ZNF740 to MEF2C. Allele G shows a higher affinity to the TFs in the induced cells. The increased expression of MEF2C leads to an increased expression of TF MEF2C's target genes, subsequently affecting the differentiation. Although genomic variation should not be a dominant factor in differentiation, we believe that genomic variation could indeed play a role in the differentiation from stem cells into trophoblast.

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“…At the somatic DMR of the Meg3 lncRNA gene at the Dlk1-Dio3 imprinted domain, the KRAB domain zinc finger protein ZFP281 facilitates promoter activity on the maternal chromosome both in embryonic and trophoblast cells. It recruits MLL protein complexes to the chromatin, which brings about H3K4me3, and also interacts with AFF3, a component of the transcription elongation complex [103][104][105].…”

Section: Protection Of Icrs Against De Novo Dna Methylationmentioning

confidence: 99%

Stability and Lability of Parental Methylation Imprints in Development and Disease

Farhadova

Gómez-Velázquez

Feil

2019

Genes

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DNA methylation plays essential roles in mammals. Of particular interest are parental methylation marks that originate from the oocyte or the sperm, and bring about mono-allelic gene expression at defined chromosomal regions. The remarkable somatic stability of these parental imprints in the pre-implantation embryo—where they resist global waves of DNA demethylation—is not fully understood despite the importance of this phenomenon. After implantation, some methylation imprints persist in the placenta only, a tissue in which many genes are imprinted. Again here, the underlying epigenetic mechanisms are not clear. Mouse studies have pinpointed the involvement of transcription factors, covalent histone modifications, and histone variants. These and other features linked to the stability of methylation imprints are instructive as concerns their conservation in humans, in which different congenital disorders are caused by perturbed parental imprints. Here, we discuss DNA and histone methylation imprints, and why unravelling maintenance mechanisms is important for understanding imprinting disorders in humans.

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Zfp281 Shapes the Transcriptome of Trophoblast Stem Cells and Is Essential for Placental Development

Cited by 33 publications

References 64 publications

Zfp281 orchestrates interconversion of pluripotent states by engaging Ehmt1 and Zic2

Zfp281 orchestrates interconversion of pluripotent states by engaging Ehmt1 and Zic2

Effect for Human Genomic Variation During the BMP4-Induced Conversion From Pluripotent Stem Cells to Trophoblast

Stability and Lability of Parental Methylation Imprints in Development and Disease

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