Disease relevance of HLTF

• In further studies of primary colon cancer tissues, HLTF methylation was detected in 27 of 63 cases (43%) [1].
• No methylation of HLTF was detected in breast or lung cancers, suggesting selection for HLTF methylation in colonic malignancies [1].
• Antiserum raised against HIP116 recognizes a 116-kDa nuclear protein in Western blots and specifically supershifts SV40 and HIV-1 protein-DNA complexes in gel shift experiments [2].
• We have isolated a human cDNA clone encoding HIP116, a protein that binds to the SPH repeats of the SV40 enhancer and to the TATA/inhibitor region of the human immunodeficiency virus (HIV)-1 promoter [2].
• We evaluated the role of HLTF promoter hypermethylation in gastric cancer [3].

High impact information on HLTF

• Loss of HLTF expression accompanied by HLTF promoter methylation was noted in nine of 34 colon cancer cell lines [1].
• Transfection of HLTF suppressed 75% of colony growth in each of three different HLTF-deficient cell lines, but showed no suppressive effect in any of three HLTF-proficient cell lines [1].
• These findings show that HLTF is a common target for methylation and epigenetic gene silencing in colon cancer and suggest HLTF is a candidate colon cancer suppressor gene [1].
• In these cell lines HLTF expression was restored by treatment with the demethylating agent 5-azacytidine [1].
• A helicaselike transcription factor (HLTF) belonging to the SWI2/SNF2 family of proteins binds to the PCS and a partly homologous sequence in the enhancer region of the LCR hypersensitive site 2 (HS2) [4].

Chemical compound and disease context of HLTF

• Helicase-like transcription factor (HLTF), a member of the SWI/SNF (mating type switching/sucrose nonfermenting) chromatin-remodeling complex, is recently found to be inactivated by promoter hypermethylation in human colorectal cancer [3].

Biological context of HLTF

• Two Sp1 sites that are also conserved in the putative promoter of human SMARCA3 and a RUSH binding site (-616/-611) that is unique to the rabbit promoter repress basal transcription [5].
• HLTF gene silencing in human colon cancer [1].
• Mutations affecting either the Sp1/Sp3 or the two HLTF sites inhibited by 6- and 2.5-fold, respectively, transient expression in HeLa cells of a reporter gene fused to the PAI-1 promoter [6].
• Here we report the characterization of the Zbu1 gene, also known as HIP116, located on human chromosome band 3q25, which encodes a DNA-binding member of this superfamily [7].
• The developmental profile of Zbu1 gene expression and the association of the protein with a tissue-specific transcriptional regulatory element distinguish it from other members of the SWI2/SNF2 family and suggest novel roles for the Zbu1 gene product [7].

Anatomical context of HLTF

• During mouse embryogenesis, Zbu1 transcripts are detected relatively late in fetal development and increase in neonatal stages, whereas the protein accumulates asynchronously in heart, skeletal muscle, and brain [7].
• Two HLTF proteins differing in translation start site (Met-1 or Met-123) were obtained by in vitro translation in reticulocyte lysate or by immunoprecipitation from HeLa cell nuclear extracts [8].
• Methylation pattern of HLTF gene in digestive tract cancers [9].
• CONCLUSIONS: Colorectal cancers without lymph node metastasis frequently exhibited the aberrant methylation of HLTF , SOCS-1 , and CDH13 genes [10].

Associations of HLTF with chemical compounds

• Early expression of the Helicase-Like Transcription Factor (HLTF/SMARCA3) in an experimental model of estrogen-induced renal carcinogenesis [11].
• Bisulfite DNA sequencing of the promoter region of HLTF showed that the CpG island was densely methylated in cell lines and cancer samples; this also appeared to correlate with expression level [3].

Physical interactions of HLTF

• Basal expression of the human plasminogen activator inhibitor-1 (PAI-1) is mediated by a promoter element named B box that binds the helicase-like transcription factor (HLTF), homologous to SNF/SWI proteins [6].

Regulatory relationships of HLTF

• In vitro transcription from the PAI-1 promoter in HeLa cell extracts was inhibited by HLTF antibodies and by the HLTF DNA binding domain [8].

Other interactions of HLTF

• Functional interactions between Sp1 or Sp3 and the helicase-like transcription factor mediate basal expression from the human plasminogen activator inhibitor-1 gene [6].

Analytical, diagnostic and therapeutic context of HLTF

• Electrophoretic mobility shift assays performed on a set of B box point mutants demonstrated two HLTF sites flanking and partially overlapping with a GT box binding Sp1 and Sp3 [6].
• Expression of HLTF was examined by reverse-transcription (RT)-polymerase chain reaction (PCR), and promoter hypermethylation in HLTF was determined by methylation-specific PCR [3].
• Sequence analysis indicates that the P113 is highly homologous to HIP116/HLTF (human) and RUSH-1alpha (rabbit) [12].
• HLTF expression was conserved in the HKT-1097 cell line established from kidney tumors, but again only 10% of positive cells were found in xenografts produced by HKT-1097 cells in nude mice [11].

References