EID1 encodes a transcriptional regulatory protein that has been implicated in cell differentiation and negative regulation of transcription. It enables histone acetyltransferase binding activity and acting upstream of or within the negative regulation of transcription by RNA polymerase II.
Structure
EID1 is a protein-coding gene whose product is assigned to the EID family.
EID1 is a broadly expressed human gene that does not show strong restriction to a single tissue. Its RNA expression pattern is classified as low tissue specificity, placing it among genes detected across many tissue contexts such as the heart, skeletal muscle, pancreas, brain, testis, etc.
EID1 is also grouped with predicted intracellular proteins, which is consistent with its assignment as a non-secreted cellular regulatory protein.
Subcellular localization
The EID1 protein is in both the nucleus and the cytoplasm. It is further localized to the nucleoplasm and to cytoplasmic ribonucleoprotein granules.
Post-translational regulation
EID1 is subject to post-translational regulation through ubiquitin-dependent proteolysis. The protein contains a modular peptidic degron that is recognized by an SCF ubiquitin ligase complex whose substrate-recognition component is FBOX21.
This complex mediates polyubiquitylation of EID1 and is necessary for efficient degradation of the protein in both proliferating and quiescent cells.
EID1 is described as unstable and short-lived, also that its degradation is especially pronounced in G0 cells. It was further reported that the degron overlaps in part with the RB1-binding domain of EID1, raising the possibility that binding interactions and protein turnover are automatically connected.
Myoblast differentiation
Studies have implicated EID1 as in control of myogenic differentiation. A study of the Prader-Willi syndrome protein necdin identified a direct interaction between necdin and EID1. In that study, EID1 was described as suppressing transcriptional activation of genes required for myoblast differentiation, while necdin promoted differentiation by binding EID1 and relieving its repression of MyoD-dependent transcription. It was also reported that EID1 is degraded in myoblasts as cells exit the cell cycle, which further links the regulation of EID1 abundance to the progression of muscle differentiation.
Studies in mice
The role of EID1 in the brain has been investigated using Eid1-knockout mouse models. In one transcriptomic study, RNA sequencing of the Eid1-knockout mouse brain identified 2,531 genes with altered expression compared to the wild-type brain, and a follow-up qRT-PCR was used to confirm the reliability of the sequencing data. Based on the changes, it was proposed that EID1 links cell proliferation in the brain.
Orthologs of EID1 have been identified in other mammals, including the rat gene Eid1, indicating that the gene is conserved across species.
Relations
EID3 shares homology with a region of EID1 implicated in CBP/p300 binding. EID1 and EID3 both function as inhibitors of CBP/p300-dependent transcription in a tissue-specific manner.
EID2 was identified as a second family member and was described as a homolog of EID1 with inhibitory effects on MyoD-dependent transcription and muscle differentiation.
Nuclear receptor interactions
EID1 has been identified as an interacting partner of the orphan nuclear receptor SF-1. EID1 was reported to suppress SF-1 mediated transactivation, indicating that EID1 can modulate transcriptional output downstream of steroidogenic factor signaling. The same study found that the inhibitory effect was not reproduced with several other nuclear receptors, including LRH-1, ERRy, and mCAR, which suggests a degree of specificity in the interaction between EID1 and SF-1.
↑"Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
↑"Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
↑Carim L, Sumoy L, Andreu N, Estivill X, Escarceller M (June 2000). "Identification and expression analysis of C15orf3, a novel gene on chromosome 15q21.1→q21.2". Cytogenetics and Cell Genetics. 88 (3–4): 330–332. doi:10.1159/000015523. PMID10828624. S2CID27139235.
↑Bush JR, Wevrick R (November 2008). "The Prader-Willi syndrome protein necdin interacts with the E1A-like inhibitor of differentiation EID-1 and promotes myoblast differentiation". Differentiation; Research in Biological Diversity. 76 (9): 994–1005. doi:10.1111/j.1432-0436.2008.00281.x. PMID18557765.
12Fu X, Luo L, Yi R, Ding B, Wang C, Zhang W, etal. (October 2019). "Transcriptome profiling in Eid1-KO mice brain shows that Eid1 links cell proliferation in the brain". Gene. 717 143998. doi:10.1016/j.gene.2019.143998. PMID31381951.
Wen H, Ao S (2001). "Identification and characterization of a novel human cDNA encoding a 21 kDa pRb-associated protein". Gene. 263 (1–2): 85–92. doi:10.1016/S0378-1119(00)00585-0. PMID11223246.
