Disease relevance of TFCP2

• We report that both YY1 and LSF participate in the formation of a complex that recognizes the initiation region of the HIV-1 LTR [1].
• YY1 and LSF may establish transcriptional and virological latency of HIV, a state that has recently been recognized in vivo and has significant implications for the long-term treatment of AIDS [2].
• RESULTS: After exposure to any of 4 different polyamides that specifically block HDAC-1 recruitment by LSF to the HIV promoter, replication-competent HIV was recovered from cultures of resting CD4+ T cells in 6 of 8 HIV-infected patients whose viremia had been suppressed by therapy [3].
• The transcription factor LSF, identified as a HeLa protein that binds the simian virus 40 late promoter, recognizes direct repeats with a center-to-center spacing of 10 bp [4].
• In addition to its role in regulating SAA3 gene expression, we provide evidence that SEF could also bind in a sequence-specific manner to the promoters of the alpha(2)-macroglobulin and Aalpha-fibrinogen genes and to an intronic enhancer of the human Wilm's tumor 1 gene, suggesting a functional role in the regulation of these genes [5].

Psychiatry related information on TFCP2

• The transcriptional factor LBP-1c/CP2/LSF gene on chromosome 12 is a genetic determinant of Alzheimer's disease [6].
• We studied whether pretreatment levels of learned helplessness (LH) were related to outcomes for substance-dependent individuals receiving high-structure, behaviorally oriented (HSB) or low-structure, facilitative (LSF) treatment [7].

High impact information on TFCP2

• Surprisingly, CP1, CP2, and NF-I each appear to recognize their binding site with highest affinity as a multisubunit complex composed of heterologous subunits [8].
• Mitogenic stimulation of resting T cells causes rapid phosphorylation of the transcription factor LSF and increased DNA-binding activity [9].
• This modulation of LSF-DNA-binding activity as T cells progress from a resting to a replicating state reveals that LSF activity is regulated during cell growth and suggests that LSF regulates growth-responsive promoters [9].
• This serum-induced CCAAT factor also bound CCAAT sequences from other promoters, for example, those of human heat shock protein 70, human c-Ha-ras, and human histone 1, but not to the adenovirus origin of replication or the SV40 enhancer core sequence, suggesting that it was related to CP1 or CP2 [10].
• LSF activates transcription from the SV40 late promoter in vitro from initiation site L325, via its binding to the template DNA [11].

Chemical compound and disease context of TFCP2

• The only significant difference in toxicities occurring through the eighth dose of IL-2 was in the maximum elevation of serum creatinine (mean, 1.7 +/- 0.8 for placebo versus 1.5 +/- 0.6 mg/dl for LSF, P = 0.013) [12].
• RESULTS: Loss of consciousness was accurately monitored by BIS, SEMG and SEF 95%, and propofol drug effect by BIS only [13].

Biological context of TFCP2

• Further, expression of a dominant-negative mutant of LSF (dnLSF), which inhibits LSF occupancy and LTR repression, results in acetylation and decreased HDAC1 occupancy at nuc 1 [14].
• The transcription factors YY1 and LSF cooperate in repression of transcription from the HIV-1 long terminal repeat (LTR) [2].
• LSF recruits YY1 to the LTR via the zinc fingers of YY1 [2].
• The Psc2 cDNA contained an open reading frame homologous to CP2 family proteins [15].
• We find that LSF binds the LTR as a tetramer and that binding is regulated by phosphorylation mediated by mitogen-activated protein kinases (MAPKs) [16].

Anatomical context of TFCP2

• Binding of CP2 to the SSE requires a heterodimeric partner present in K562 cells [17].
• The absence of the A allele was associated with a lower LBP-1c/CP2/LSF gene expression in lymphocytes from AD cases compared with controls [6].
• These experiments demonstrated that the various isoforms of CP2/LSF/LBP1 are differently distributed among subcellular fractions [18].
• Although ubiquitously expressed, the transcriptional factor CP2 also exhibits some tissue- or stage-specific activation toward certain genes such as globin in red blood cells and interleukin-4 in T helper cells [19].
• Overall data indicate that CP2 is a major factor in the regulation of globin expression in human and mouse erythroid cells, and CP2 binding to the globin gene promoter is essential for the enhanced transcription of globin genes in erythroid differentiation [20].

Associations of TFCP2 with chemical compounds

• Glutathione S-transferase pull-down and coimmunoprecipitation assays showed that two HXPR motif-containing proteins REST and YY1 indeed were able to bind CP2 [19].
• Four guanine residues within the LSF-GC site, when methylated, strongly interfere with LSF binding [11].
• LSF binds specifically to the 21-base-pair repeats of the SV40 promoters, forming specific protein-DNA complexes, which migrate more rapidly through nondenaturing polyacrylamide gels than that formed by the previously identified transcription factor Sp1 [21].
• Double labeling experiments with CP1 and CP2, respectively, and a murine anti-chymase mAb demonstrated the presence of HMC-CP in the tryptase-positive, chymase-positive mast cell type (MCTC) only [22].
• CT1501R (lisofylline; LSF) is one of several methyl xanthine congeners that inhibit the effects of TNF by the interruption of specific signal transduction pathways [12].

Physical interactions of TFCP2

• Using an epitope-counting method, we show that LSF binds DNA as a homodimer [4].

Regulatory relationships of TFCP2

• The human factors YY1 and LSF repress the human immunodeficiency virus type 1 long terminal repeat via recruitment of histone deacetylase 1 [2].
• Data from immunoprecipitation and transient transfection assays demonstrated that SEF and Sp1 interacted in vitro and may act together in vivo to regulate PAX6 expression [23].

Other interactions of TFCP2

• 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 [17].
• Activation of the human PAX6 gene through the exon 1 enhancer by transcription factors SEF and Sp1 [23].
• Here, we propose that a genetic variation in the transcriptional factor LBP-1c/CP2/LSF gene, located close to the LRP locus, is a genetic susceptibility factor for AD [6].
• To further elucidate its role in the regulation of the SAA3 gene, we purified SEF from HeLa nuclear extracts to near homogeneity by using conventional liquid chromatography and DNA affinity chromatography [5].
• CP2 analogs represent a new class of promising compounds for the amelioration of Abeta toxicities within both intracellular and extracellular sites [24].

Analytical, diagnostic and therapeutic context of TFCP2

• Although addition of anti-CP2 antiserum disrupts the formation of the SSP-SSE complex in the electrophoretic mobility shift assay (EMSA), recombinant CP2 fails to bind to the SSE [17].
• Co-immunoprecipitation experiments demonstrated that the interaction between Fe65 and CP2/LSF/LBP1 also takes place in vivo between the native molecules [18].
• Sequence analysis of this clone revealed that this ligand corresponded to the previously identified transcription factor CP2/LSF/LBP1 [18].
• Molecular cloning of the alpha-globin transcription factor CP2 [25].
• Recent functional imaging and electrical stimulation studies have localized in humans two frontal regions critical for the production of saccadic and anti-saccadic eye movements: the frontal and supplementary eye fields (FEF and SEF, respectively) [26].

References