Chromatin Landscape Instructs Precise Transcription Factor Regulome during Embryonic Lineage Specification [CUT&RUN]
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE250176 | GEO | 2024/04/01
REPOSITORIES: GEO
Similar Datasets
Project description:Embryos originate from fertilized eggs and are shaped through continuous cell division and differentiation, accompanied by dramatic changes in transcription, translation, and metabolism. Epigenetic information and transcription factors (TFs) play indispensable roles in regulating these processes. Recently, the trophoblast regulator TFAP2C was found to be essential in initiating the earliest cell fate decisions. However, Tfap2c transcripts are still detectable in both the inner cell mass (ICM) and trophectoderm (TE) of blastocysts, raising questions regarding how TFAP2C functions once these two lineages are established. In this study, we delineated the dynamics of TFAP2C during the mouse peri-implantation stage and elucidated its collaboration with the key lineage regulators CDX2 and NANOG. Importantly, we proposed 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, this research highlights the plasticity of the epigenetic environment in designating the genomic binding of highly adaptable lineage-specific TFs and regulating embryonic cell fates.
2024-04-07 | GSE250177 | GEO
Project description:In mammals, early lineage specification originates from the establishment of cell polarization in early embryos, before providing the foundation for all somatic development. Although there have been heated debates about whether transcription factors (TFs) or epigenetic information plays the dominant role in cell fate decisions, the precise annotation of TFs remains largely elusive in early embryos, restricting the functional study of developmentally important TFs. Here, we investigated the genome-wide landscapes of two known triggers of mouse embryo polarization: transcription factor AP-2 gamma (Tfap2c) and TEA domain transcription factor 4 (Tead4). We found that Tfap2c can bridge the connection between the promoter and the proximal enhancer, and further facilitate the functions of downstream Tead4 and Klf5 in boosting polarization. Our study also implicated that Rarg-initiated active demethylation might be a prerequisite for proper Tfap2c functioning. Furthermore, the results demonstrated that both genomic imprinting and nucleotide polymorphism can instruct TF binding, leading to allele-specific expression in early embryos. Overall, our study characterized TF dynamics during the peri-implantation stage and revealed their spatiotemporal interactions with the epigenetic environment in driving polarization and lineage specification.
2024-03-03 | GSE212567 | GEO
Project description:In mammals, early lineage specification originates from the establishment of cell polarization in early embryos, before providing the foundation for all somatic development. Although there have been heated debates about whether transcription factors (TFs) or epigenetic information plays the dominant role in cell fate decisions, the precise annotation of TFs remains largely elusive in early embryos, restricting the functional study of developmentally important TFs. Here, we investigated the genome-wide landscapes of two known triggers of mouse embryo polarization: transcription factor AP-2 gamma (Tfap2c) and TEA domain transcription factor 4 (Tead4). We found that Tfap2c can bridge the connection between the promoter and the proximal enhancer, and further facilitate the functions of downstream Tead4 and Klf5 in boosting polarization. Our study also implicated that Rarg-initiated active demethylation might be a prerequisite for proper Tfap2c functioning. Furthermore, the results demonstrated that both genomic imprinting and nucleotide polymorphism can instruct TF binding, leading to allele-specific expression in early embryos. Overall, our study characterized TF dynamics during the peri-implantation stage and revealed their spatiotemporal interactions with the epigenetic environment in driving polarization and lineage specification.
2024-03-03 | GSE228361 | GEO
Project description:In mammals, early lineage specification originates from the establishment of cell polarization in early embryos, before providing the foundation for all somatic development. Although there have been heated debates about whether transcription factors (TFs) or epigenetic information plays the dominant role in cell fate decisions, the precise annotation of TFs remains largely elusive in early embryos, restricting the functional study of developmentally important TFs. Here, we investigated the genome-wide landscapes of two known triggers of mouse embryo polarization: transcription factor AP-2 gamma (Tfap2c) and TEA domain transcription factor 4 (Tead4). We found that Tfap2c can bridge the connection between the promoter and the proximal enhancer, and further facilitate the functions of downstream Tead4 and Klf5 in boosting polarization. Our study also implicated that Rarg-initiated active demethylation might be a prerequisite for proper Tfap2c functioning. Furthermore, the results demonstrated that both genomic imprinting and nucleotide polymorphism can instruct TF binding, leading to allele-specific expression in early embryos. Overall, our study characterized TF dynamics during the peri-implantation stage and revealed their spatiotemporal interactions with the epigenetic environment in driving polarization and lineage specification.
2024-03-03 | GSE248696 | GEO
Project description:In mammals, early lineage specification originates from the establishment of cell polarization in early embryos, before providing the foundation for all somatic development. Although there have been heated debates about whether transcription factors (TFs) or epigenetic information plays the dominant role in cell fate decisions, the precise annotation of TFs remains largely elusive in early embryos, restricting the functional study of developmentally important TFs. Here, we investigated the genome-wide landscapes of two known triggers of mouse embryo polarization: transcription factor AP-2 gamma (Tfap2c) and TEA domain transcription factor 4 (Tead4). We found that Tfap2c can bridge the connection between the promoter and the proximal enhancer, and further facilitate the functions of downstream Tead4 and Klf5 in boosting polarization. Our study also implicated that Rarg-initiated active demethylation might be a prerequisite for proper Tfap2c functioning. Furthermore, the results demonstrated that both genomic imprinting and nucleotide polymorphism can instruct TF binding, leading to allele-specific expression in early embryos. Overall, our study characterized TF dynamics during the peri-implantation stage and revealed their spatiotemporal interactions with the epigenetic environment in driving polarization and lineage specification.
2024-03-03 | GSE212566 | GEO
Project description:In mammals, early lineage specification originates from the establishment of cell polarization in early embryos, before providing the foundation for all somatic development. Although there have been heated debates about whether transcription factors (TFs) or epigenetic information plays the dominant role in cell fate decisions, the precise annotation of TFs remains largely elusive in early embryos, restricting the functional study of developmentally important TFs. Here, we investigated the genome-wide landscapes of two known triggers of mouse embryo polarization: transcription factor AP-2 gamma (Tfap2c) and TEA domain transcription factor 4 (Tead4). We found that Tfap2c can bridge the connection between the promoter and the proximal enhancer, and further facilitate the functions of downstream Tead4 and Klf5 in boosting polarization. Our study also implicated that Rarg-initiated active demethylation might be a prerequisite for proper Tfap2c functioning. Furthermore, the results demonstrated that both genomic imprinting and nucleotide polymorphism can instruct TF binding, leading to allele-specific expression in early embryos. Overall, our study characterized TF dynamics during the peri-implantation stage and revealed their spatiotemporal interactions with the epigenetic environment in driving polarization and lineage specification.
2024-03-03 | GSE212565 | GEO
Project description:During the first lineage segregation, a mammalian totipotent embryo differentiates into inner cell mass (ICM) and trophectoderm (TE). However, how transcription factors (TFs) regulate this earliest cell fate decision in vivo remains elusive, with their regulomes primarily inferred from cultured cells. Here, we investigated the TF regulomes during the first mouse lineage specification across 6 stages, spanning the pre-initiation, initiation, commitment, and maintenance phases. Unexpectedly, we found TFAP2C, a trophoblast regulator, bound and activated both early TE and ICM genes at the totipotent (2-8-cell) stages (“bipotency activation”). Tfap2c deficiency caused downregulation of early ICM genes, including Nanog, Nr5a2, Tdgf1, and early TE genes, including Tfeb and Itgb5 in 8-cell embryos. Transcription defects in both ICM and TE lineages were also found in blastocysts, accompanied by increased apoptosis and reduced cell numbers in ICMs. Upon trophoblast commitment, TFAP2C left early-ICM genes but acquired binding to late-TE genes in blastocysts where it co-bound with CDX2, and later to extra-embryonic ectoderm (ExE) genes where it cooperatively co-occupied with the former ICM regulator SOX2. Finally, “bipotency activation” in totipotent embryos also applied to a pluripotency regulator NR5A2 which similarly bound and activated both ICM and TE lineage genes at the 8-cell stage. These data reveal a unique transcription circuity of totipotency underpinned by highly adaptable lineage regulators.
2023-11-23 | GSE216256 | GEO
Project description:Cells belonging to trophoblast lineage are required for proper implantation and placentation, as well as the vascular, hematopoietic, and immunological properties of the placenta, a crucial organ mediating dynamic interactions between maternal and fetal tissues. Defects in trophoblast lineage development can cause early pregnancy failure or other pregnancy-related disorders. Despite its pivotal roles, the placenta remains as one of the least studied organs. Until now, only a handful of trophoblast-specific transcription factors (TFs) have been characterized, and underlying regulatory mechanisms modulating trophoblast lineage development remain poorly understood. Here we explore trophoblast stem cell (TSC)-specific super-enhancers (SEs) and subsequently identify SE-associated factors enriched with previously known and many unknown TFs modulating trophoblast lineage development. By mapping direct targets of 28 TSC-specific TFs in TSCs, we construct highly intertwined transcriptional regulatory networks where TFs are co-regulated and linked with signaling pathways, and which function as cellular modules dedicated to trophoblast lineage development. Additionally, we reveal that TSC-specific TFs alter their target sites corresponding to the reshaped enhancers during TSC differentiation. These findings advance our understanding on placenta biology.
2019-09-25 | GSE110950 | GEO
Project description:The germ cell lineage ensures the continuity of life through the generation of male and female gametes, which unite to form a totipotent zygote. We have established a culture system that recapitulates the mouse germ-cell specification pathway: Using cytokines, embryonic stem cells (ESCs)/induced pluripotent stem cells (iPSCs) are induced into epiblast-like cells (EpiLCs) and then into primordial germ cell-like cells (PGCLCs) with capacity both for spermatogenesis and oogenesis, creating an opportunity for understanding and regulating mammalian germ cell development in both sexes in vitro. Here we show that, without cytokines, simultaneous over-expression of three transcription factors (TFs), Blimp1 (also known as Prdm1), Prdm14 and Tfap2c (also known as AP2γ), directs EpiLCs, but not ESCs, swiftly and highly efficiently into a PGC state with endogenous transcription circuitry. The induction of the PGC state on EpiLCs minimally requires Prdm14 but not Blimp1 or Tfap2c. The TF-induced PGC state reconstitutes key transcriptome and epigenetic reprogramming in PGCs, but bypasses a mesodermal program that accompanies PGC specification in vivo and in vitro by cytokines including BMP4. Importantly, the TF-induced PGC-like cells robustly contribute to spermatogenesis and fertile offspring. Our findings provide not only a novel insight into the transcriptional logic that creates a germ cell state, but also a foundation for the TF-based reconstitution and regulation of mammalian gametogenesis. Aim of this analysis is characterization of transcription factor-induced primordial germ cells (TF-PGCLCs) compared with cytokine-induced primordial germ cells (Ck-PGCLCs) (Hayashi et al., 2011, Cell), epiblast-like cells (EpiLCs) (Hayashi et al., 2011, Cell), and embryonic stem cells (ESCs) and identification of genes differentially expressed among them. TF-PGCLCs induced by multiple combinations of TFs (Blimp1 (B), Prdm14 (P14), and Tfap2c (A) (BP14A), BP14, P14A, P14) on day 2 and 4 (for BP14A cells) of the induction were also compared. Parental clone without exogenous TFs cultured with doxycycline, are also included as a negative control. Ck-PGCLCs day 2 and day 4 samples, which are previously unreported, EpiLCs and ESCs used in this study were also included. Overexpression of exogenous three TFs in ESCs yields stella-ECFP (SC) positive cells, which were sorted and included in the analysis. cDNA samples, prepared from approximately 20,000 cells, were amplified with a quantitative global PCR method (Kurimoto et al., 2006, Nucleic Acids Research). Two biological duplicates for each cell type were analyzed. Samples from GSE30056 were also included and reanalysed (GSM1070855-GSM1070864).
2013-08-04 | E-GEOD-43775 | biostudies-arrayexpress
Project description:The ongoing ENCODE consortium represents a useful compendium of locations of TFs, chromatin marks, gene expression data. In previous reports, we identified modules of CCAAT-binding NF-Y with individual TFs. Here, we analyzed all 363 factors currently present: 68 with enrichment of CCAAT in their locations, 38 with overlap of peaks. New sequence-specific TFs, co-activators and co-repressors are reported. Co-association patterns correspond to specific targeted genes categorizations and gene expression changes, as assessed by RNA-seq after NF-Y inactivation. These data widen and better define a coherent model of synergy of NF-Y with selected groups of TFs and cofactors.
2020-12-07 | GSE151237 | GEO