The role of transcription factor Tcfap2c/TFAP2C in trophectoderm development

Kuckenberg, Peter; Kubaczka, Caroline; Schorle, Hubert

doi:10.1016/j.rbmo.2012.02.015

Cited by 71 publications

(60 citation statements)

References 94 publications

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“…Based on the e7.5 FPKM and the fold difference (e7.5 FPKM/e9.5 FPKM), the TFs most likely binding to migration enhancers at e7.5 are Fosl1, Ets2, and Tcfap2c (Figure 4). These expression-based predictions are promising, as each of the three TFs has been implicated in placental development [59–63], and Fosll has already been further implicated in trophoblast invasion [62]. Our analysis suggests that all three factors are working together to regulate trophoblast invasion, and identifies the specific enhancers to which they may bind.…”

Section: Resultsmentioning

confidence: 77%

Changes in the enhancer landscape during early placental development uncover a trophoblast invasion gene-enhancer network

2016

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Introduction Trophoblast invasion establishes adequate blood flow between mother and fetus in early placental development. However, little is known about the cis-regulatory mechanisms underlying this important process. We aimed to identify enhancer elements that are active during trophoblast invasion, and build a trophoblast invasion gene-enhancer network. Methods We carried out ChIP-Seq for an enhancer-associated mark (H3k27Ac) at two time points during early placental development in mouse. One time point where invasion is at its peak (e7.5) and another time point shortly afterwards (e9.5). We use computational analysis to identify putative enhancers, as well as the transcription factor binding sites within them, that are specific to the time point of trophoblast invasion. Results We compared read profiles at e7.5 and e9.5 to identify 1,977 e7.5-specific enhancers. Within a subset of e7.5-specific enhancers, we discovered a cell migration associated regulatory code, consisting of three transcription factor motifs: AP1, Ets, and Tcfap2. To validate differential expression of the transcription factors that bind these motifs, we performed RNA-Seq in the same context. Finally, we integrated these data with publicly available protein-protein interaction data and constructed a trophoblast invasion gene-enhancer network. Discussion The data we generated and analysis we carried out improves our understanding of the regulatory mechanisms of trophoblast invasion, by suggesting a transcriptional code exists in the enhancers of cell migration genes. Furthermore, the network we constructed highlights novel candidate genes that may be critical for trophoblast invasion.

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Section: Resultsmentioning

confidence: 77%

Changes in the enhancer landscape during early placental development uncover a trophoblast invasion gene-enhancer network

2016

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“…9A). Thus, the upregulation of Tfap2c, which is normally found during wild-type TSC differentiation [3], was absent in the mutants. The levels of both Cdx2 (Fig.…”

Section: Effects Of Tfap2c +/-On Trophoblast Stem Cell Differentiationmentioning

confidence: 85%

“…Tfap2A-E in mice and TFAP2A-E in humans are involved in balancing proliferation and differentiation in many tissues [2]. The family members Tfap2a, Tfap2b, and Tfap2c have been shown to be expressed in the trophectoderm and in all other extraembryonic derivatives [3,4].…”

Section: Introductionmentioning

confidence: 99%

Reduced Gene Dosage of Tfap2c Impairs Trophoblast Lineage Differentiation and Alters Maternal Blood Spaces in the Mouse Placenta1

Kaiser

Koch

Kühnel

et al. 2015

Biology of Reproduction

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Tfap2c is required for placental development and trophoblast stem cell maintenance. Deletion of Tfap2c results in early embryonic loss because of failure in placental development. We evaluated the effect of reduced Tfap2c expression on fetal outcome and placental development. Sixty percent of the heterozygous mice were lost directly after birth. Labyrinthine differentiation was impaired, as indicated by enhanced proliferation and inclusions of cobblestone-shaped cell clusters characterized by expression of Tfap2c and glycogen stores. Moreover, expression of marker genes such as Cdx2, Eomes, Gata3, and Ascl2 are decreased in the spongiotrophoblast and indicate a lowered stem cell potential. On Day 18.5 postcoitum, the labyrinth layer of Tfap2c(+/-) placentas exhibited massive hemorrhages in the maternal blood spaces; these hemorrhages might have contributed to the significantly reduced number of live-born pups. These morphological alterations were accompanied by a shift toward sinusoidal trophoblast giant cells as the cell subpopulation lining the maternal sinusoids and toward reduction in expression of the prolactin gene family member Prl2c2, a finding characteristic of the spiral arteries lining trophoblast cells. The trophoblast stem cells heterozygous for Tfap2c exhibited a reduction in the expression level of stem cell markers and in their proliferation and differentiation capacity but did not exhibit changes in marker genes of the trophoblast giant cell lineage. Taken together, these findings indicate that a reduction in the gene dosage of placental Tfap2c leads to morphological changes in the labyrinth at midgestation and in the maternal blood spaces during late pregnancy.

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“…By regulating the expression of many downstream genes, TFAP2C mediates various cellular processes, including induction, differentiation, survival, proliferation and apoptosis under diverse developmental contexts (50)(51)(52)(53)(54). The internalization of activated EGFR involves the AP-2 complex (55).…”

Section: Discussionmentioning

confidence: 99%

Genome-wide profiling of long non-coding RNA expression patterns in the EGFR-TKI resistance of lung adenocarcinoma by microarray

et al. 2016

Oncology Reports

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Abstract. Mutations in the epidermal growth factor receptor (EGFR) make lung adenocarcinoma cells sensitive to EGFR tyrosine kinase inhibitors (TKIs). Long-term cancer therapy may cause the occurrence of acquired resistance to EGFR TKIs. Long non-coding RNAs (lncRNAs) play important roles in tumor formation, tumor metastasis and the development of EGFR-TKI resistance in lung cancer. To gain insight into the molecular mechanisms of EGFR-TKI resistance, we generated an EGFR-TKI-resistant HCC827-8-1 cell line and analyzed expression patterns by lncRNA microarray and compared it with its parental HCC827 cell line. A total of 1,476 lncRNA transcripts and 1,026 mRNA transcripts were dysregulated in the HCC827-8-1 cells. The expression levels of 7 chosen lncRNAs were validated by real-time quantitative PCR. As indicated by functional analysis, several groups of lncRNAs may be involved in the bio-pathways associated with EGFR-TKI resistance through their cis-and/or trans-regulation of protein-coding genes. Thus, lncRNAs may be used as novel candidate biomarkers and potential targets in EGFR-TKI therapy in the future.

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The role of transcription factor Tcfap2c/TFAP2C in trophectoderm development

Cited by 71 publications

References 94 publications

Changes in the enhancer landscape during early placental development uncover a trophoblast invasion gene-enhancer network

Changes in the enhancer landscape during early placental development uncover a trophoblast invasion gene-enhancer network

Reduced Gene Dosage of Tfap2c Impairs Trophoblast Lineage Differentiation and Alters Maternal Blood Spaces in the Mouse Placenta1

Genome-wide profiling of long non-coding RNA expression patterns in the EGFR-TKI resistance of lung adenocarcinoma by microarray

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