E2F4 is a member of the E2F family of transcription factors. E2F4 binds DNA cooperatively with DP proteins through the E2 recognition site, 5'-TTTC[CG]CGC-3' found in the promoter region of a number of genes whose products are involved in cell cycle regulation or in DNA replication []. In growth arrested cells, transcriptional activity by E2Fs is repressed by retinoblastoma (RB) proteins. E2F-4 can bind to RB and related proteins p130 to p107 [].
This entry represents protein LIN-9/ALWAYS EARLY (LIN-9/ALY). LIN-9 from Caenorhabditis elegans is a homologue of the Drosophila always early (ALY) protein, which functions as a repressor of cell cycle regulated genes [, ].LIN-9 is a component of the evolutionary conserved DREAM (MuvB/DRM) complex, which represses transcription []. DREAM complex undergoes a cell cycle dependent switch of subunits. DREAM core bindsto the E2F4 transcription factor and to the RBL2 (p130) in quiescent cells, while associates with the transcription factor B-MYB in the S-phase []. In humans, LIN-9 acts as a tumor suppressor and plays a role in the expression of genes required for the G1/S transition [, ]. In pluripotent embryonic stem cells (ESC), LIN-9 plays an important role for proliferation and genome stability by activating genes with important functions in mitosis and cytokinesis [].In Arabidopsis thaliana, ALY is expressed ubiquitously in vegetative and reproductive tissues [].
This entry includes Host cell factor 1 (HCF1) and Host cell factor 2 (HCF2) from humans. They contain an N-terminal kelch domain and a C-terminal FnIII domain. However, HCF2 is smaller than HCF-1, lacking the complete central region including the HCF1 specific repeats and as a result is not subject to proteolytic processing []. This entry also includes their Drosophila melanogaster homologue, dHCF, which is involved in both activation and repression of transcription during fly development []. Host cell factor homologue hcf-1 from C. elegans controls the cell cycle through mitotic histone phosphorylation modulation and negatively regulates responses to environmental stresses [].HCF1 is associated with the activation and repression of gene expression. It is brought to specific promoters by association with DNA-sequence-specific transcription factors such as Sp1, GABP, YY1, Ronin/THAP11, and E2F1 and E2F4 []. HCFC1 recruits and is a part of several different complexes, including the SET1 histone methyltransferase complex (transcription activation), the SIN3 histone deacetylase complex (transcription repression) [], the THAP1/THAP3-HCFC1-OGT complex (required for the regulation of the transcriptional activity of RRM1) [], and the NSL complex (acetylation of nucleosomal histone H4) [].HCF2 is involved in activation of differentiation and morphogenesis gene expression programs, and in parallel in inhibition of cellular growth and metabolism [].
Host cell factor 1 (HCFC1) is associated with the activation and repression of gene expression. It is brought to specific promoters by association with DNA-sequence-specific transcription factors such as Sp1, GABP, YY1, Ronin/THAP11, and E2F1 and E2F4 []. HCFC1 recruits and is a part of several different complexes, including the SET1 histone methyltransferase complex (transcription activation), the SIN3 histone deacetylase complex (transcription repression) [], the THAP1/THAP3-HCFC1-OGT complex (required for the regulation of the transcriptional activity of RRM1) [], and the NSL complex (acetylation of nucleosomal histone H4) []. This entry includes mammalian HCFC1 and the Drosophila homologue, dHCF. They undergo a process of proteolytic maturation to produce a heterodimeric complex of HCF-N and HCF-C subunits, by different enzymes, O-GlcNAc transferase and taspase1, respectively [, ]. They share a Kelch domain, regions biased for basic (Basic) or acidic (Acidic) amino acids, fibronectin type 3 repeats, and a nuclear localization signal [].During human herpes simplex virus infection, HCFC1 forms a multiprotein-DNA complex enabling transcription of the virus's early genes []. It is also a co-activator of EGR2/Krox20 []and the GA-binding protein GABP2 [], and represses ZBTB17/Miz-1 [].
