DPPA4 Human
Description
Functional Roles in Pluripotency and Development
Epigenetic Regulation
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Binds GC-rich regions and CpG islands, maintaining active chromatin states at developmental gene promoters (e.g., YES1, FGF4, UTF1) .
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Modifies histone marks (e.g., H3K9me3) to prevent repressive chromatin formation .
Interaction Network
Key partners include:
Role in Zygotic Genome Activation (ZGA)
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Directly binds Dux promoter to initiate ZGA in embryos and 2C-like stem cells .
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Regulates LINE-1 retrotransposons, which modulate chromatin accessibility during early development .
Oncogenic and Disease Associations
Cancer Implications
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Overexpressed in cancers, promoting cell cycle progression via:
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Associates with poor prognosis in multiple cancers (Protein Atlas) .
Chemical Interactions
| Compound | Effect on DPPA4 | Source |
|---|---|---|
| Valproic acid | Decreases mRNA expression | RGD |
| Benzo[a]pyrene | Alters promoter methylation | RGD |
| All-trans-retinoic acid | Reduces expression | RGD |
Regulatory Mechanisms and Disease Models
Developmental Studies
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Maternal DPPA4 is dispensable for ZGA but essential for offspring survival, suggesting epigenetic priming of developmental genes .
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Loss of DPPA2/4 in embryonic stem cells reduces LINE-1 and MERVL retrotransposon activity, impairing pluripotency .
Therapeutic Potential
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Target for reprogramming somatic cells to induced pluripotent stem cells (iPSCs) .
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Biomarker for early embryogenesis defects and cancer progression .
Research Gaps and Future Directions
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Isoform-Specific Functions: Human DPPA4 isoforms and their roles in development/cancer remain uncharacterized.
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Mechanistic Insights: Structural basis of DPPA4-DNA binding and crosstalk with other epigenetic modifiers (e.g., HDACs) .
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Clinical Translation: Development of DPPA4 inhibitors for cancer therapy requires further validation.
Product Specs
Q&A
Basic Research Questions
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What is DPPA4 and what is its general function in human pluripotent cells?
DPPA4 (Developmental Pluripotency-Associated 4) is a nuclear protein that has been identified through multiple high-profile screens as a gene expressed exclusively in pluripotent cells . The protein contains an SAP-like domain and associates preferentially with transcriptionally active chromatin . In mouse studies, DPPA4 has been shown to activate transcription of genes important for germ cell development and is essential for murine embryogenesis .
The human DPPA4 ortholog shares significant structural and functional characteristics with its mouse counterpart, including the conserved SAP (SAF-A/B, Acinus, and PIAS) motif for DNA binding and a C-terminal domain of unknown function . Based on mouse studies, we can infer that human DPPA4 likely functions as a regulator of pluripotency-associated gene networks and may play roles in modulating chromatin accessibility and transcriptional activation of developmental genes.
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How is DPPA4 expression regulated during human development?
The expression pattern of DPPA4 is exquisitely regulated during development. Based on mouse studies, DPPA4 transcripts are present at fertilization through maternal inheritance and remain expressed throughout pre-implantation development, with dynamic regulation of different isoforms . In mice, two DPPA4 isoforms have been detected: low levels of the full-length form in oocytes and zygotes, and a form lacking the SAP domain expressed from zygotic genome activation (ZGA) to blastocyst stage .
In human contexts, DPPA4 expression similarly appears restricted to pluripotent cells, including embryonic stem cells and induced pluripotent stem cells. Its expression is downregulated upon differentiation, making it a valuable marker for pluripotency. Regulatory mechanisms likely involve epigenetic modifications, particularly since DPPA4 associates with CpG islands, which are often modulated by DNA methylation .
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What is the relationship between DPPA4 and DPPA2 in the context of human stem cell research?
DPPA4 and DPPA2 are paralog proteins that appear to function cooperatively in pluripotent cells. Mouse studies demonstrate that DPPA2 and DPPA4 can heterodimerize and are best recruited jointly to target genes . Both proteins bind to the 5' region of genes they regulate, including Dux, and are less efficiently recruited to these targets when one of the paralogs is absent .
In human stem cell research, this relationship suggests that both factors should be studied in concert rather than in isolation. Experimental approaches that target only one factor may yield incomplete results due to potential compensatory or cooperative functions. The co-expression and potential heterodimerization of these proteins indicate they likely constitute a functional unit in regulating pluripotency-associated genes in human cells, similar to their function in mouse cells.
Product Science Overview
Developmental Pluripotency Associated 4 (DPPA4) is a protein-coding gene that plays a crucial role in maintaining the pluripotency of stem cells. It is one of the core pluripotency genes, although its molecular and cellular functions are not yet fully understood . DPPA4 is associated with various pathways, including RNA Polymerase I Promoter Opening and the transcriptional regulation of pluripotent stem cells .
DPPA4 was identified as a key factor in the maintenance of pluripotency in embryonic stem cells. It is particularly significant in the context of developmental biology and regenerative medicine due to its role in maintaining the undifferentiated state of stem cells . The protein is also implicated in various diseases, including prostate cancer and astigmatism .
Recent studies have shed light on the molecular functions of DPPA4. It has been found to interact with ERBB3-binding protein 1 (EBP1), a growth factor signaling mediator. This interaction is crucial for the transcriptional regulation of pluripotent cells. DPPA4 preferentially binds to the p48 isoform of EBP1 in pluripotent cells, and this interaction is reduced upon differentiation . The interaction between DPPA4 and EBP1 is mediated by the highly conserved SAF-A/B, Acinus, and PIAS (SAP) domain .
DPPA4 is also involved in epigenetic regulation. Genome-wide DNA methylation analysis has shown that the regulatory region of DPPA4 is hypomethylated in early alcohol-exposed placentas . This hypomethylation is associated with altered regulation of DPPA2, a closely linked heterodimer of DPPA4 . These findings suggest that DPPA4 plays a role in the epigenetic changes induced by prenatal alcohol exposure, which can lead to developmental disorders .
