Disease relevance of NF-E4

• Enforced expression of NF-E4 in K562 cells and primary erythroid progenitors induces endogenous fetal globin gene expression, suggesting a possible strategy for therapeutic intervention in the hemoglobinopathies [1].

High impact information on NF-E4

• Western analysis of partially purified NF-E4 using anti-CP2 antiserum or the NF-E4 monoclonal antibody both demonstrate a dominant band at 66 kDa [2].
• The NF-E4 gene encodes a 22-kDa polypeptide employing a non-AUG initiation codon [3].
• Repression of human gamma-globin gene expression by a short isoform of the NF-E4 protein is associated with loss of NF-E2 and RNA polymerase II recruitment to the promoter [3].
• Antisera specific to NF-E4 detects this species and an additional 14 kDa protein, which initiates from an internal methionine [3].
• Induction of human fetal globin gene expression by a novel erythroid factor, NF-E4 [1].

Biological context of NF-E4

• Acetylation of NF-E4 is restricted to a single residue (Lys(43)) in the amino-terminal domain of the protein and results in two important functional consequences [4].
• Using the protein dimerization domain of CP2 in a yeast two-hybrid screen, we have cloned a novel gene, NF-E4, encoding the tissue-restricted component of the SSP [1].
• To examine the role of NF-E4 in an in vivo model of hemoglobin switching, we enforced the expression of p22 NF-E4 in transgenic mice carrying the human beta-globin locus yeast artificial chromosome [5].

Anatomical context of NF-E4

• We have studied the role of acetylation in the regulation of the transcription factor NF-E4, a component of a protein complex that facilitates the preferential expression of the human gamma-globin genes in fetal erythroid cells [4].
• NF-E4 is expressed in fetal liver, cord blood, and bone marrow and in the K562 and HEL cell lines, which constitutively express the fetal globin genes [1].

Regulatory relationships of NF-E4

• Site-specific acetylation of the fetal globin activator NF-E4 prevents its ubiquitination and regulates its interaction with the histone deacetylase, HDAC1 [4].

Other interactions of NF-E4

• We have shown that NF-E4 interacts directly with, and serves as a substrate for, the acetyltransferase co-activator PCAF [4].
• Acetylation of Lys(43) also reduces the interaction between NF-E4 and HDAC1, potentially maximizing the activating ability of the factor at the gamma-promoter [4].
• SSP binds to the chicken SSE and formation of this complex is ablated by the addition of anti-CP2 antiserum or a monoclonal antibody to NF-E4 [2].

References