HGNC Approved Gene Symbol: THAP7
Cytogenetic location: 22q11.21 Genomic coordinates (GRCh38): 22:20,999,104-21,002,118 (from NCBI)
By searching databases, Roussigne et al. (2003) identified several proteins containing an N-terminal THAP domain, including THAP7. The THAP domain of the deduced 309-amino acid THAP7 protein includes a C2CH signature, an AVPTIF box, and several other conserved amino acids.
Using TAF1B (604904) as bait in a yeast 2-hybrid screen of a vascular smooth muscle cell cDNA library, Macfarlan et al. (2005) cloned THAP7. The deduced 309-amino acid protein contains an N-terminal THAP domain, followed by a proline-rich region and a C-terminal acidic domain. Northern blot analysis detected ubiquitously expressed THAP7 transcripts of 1.2, 1.3, and 1.6 kb, with highest expression in testis. mRNA dot blot analysis detected THAP7 expression in all tissues and cell lines examined, with highest expression in testis. THAP7 was overexpressed in a leukemia cell line.
Macfarlan et al. (2005) found that THAP7 bound to histones H3 (see 142780) and H4 (see 602822), but not to histones H2A (see 613499) or H2B (see 609904). Mutation analysis indicated that the acidic domain of THAP7 bound to the N-terminal histone tails of histones H3 and H4, and it bound to histone tails contained within 293T human embryonic kidney cell nucleosomes in vitro. THAP7 bound to all histone H3 tail peptides tested, including peptides that were mono-, di-, tri-, or tetraacetylated, as well as peptides modified by phosphorylation or methylation. However, THAP7 only bound histone H4 peptides that were unmodified, mono-, or diacetylated, and not to H4 peptides that were tri- or tetraacetylated. THAP7 localized primarily to the nucleus in several cell lines, and it was found in the soluble nuclear fraction and chromatin fraction of disrupted 293T cells. In chromatin association assays, THAP7 bound less tightly to hyperacetylated chromatin than to hypoacetylated chromatin, and the C-terminal acidic domain was required for chromatin binding. Coimmunoprecipitation and pull-down assays showed that THAP7 interacted with HDAC3 (605166) and with NCOR (see NCOR1; 600849) in 293T cell nuclear lysates. THAP7 repressed basal transcription when targeted to a reporter promoter, and mutation analysis indicated that the THAP and acidic domains mediated transcriptional repression. Macfarlan et al. (2005) found a significant increase in HDAC3 and NCOR recruitment to the promoter region of a chromosomally integrated THAP7-repressed reporter. They hypothesized that THAP7 represses transcription by recruiting HDAC3 and NCOR to promoters to deacetylate histone H3.
The International Radiation Hybrid Mapping Consortium mapped the THAP7 gene to chromosome 22 (RH15764).
Macfarlan, T., Kutney, S., Altman, B., Montross, R., Yu, J., Chakravarti, D. Human THAP7 is a chromatin-associated, histone tail-binding protein that represses transcription via recruitment of HDAC3 and nuclear hormone receptor corepressor. J. Biol. Chem. 280: 7346-7358, 2005. [PubMed: 15561719] [Full Text: https://doi.org/10.1074/jbc.M411675200]
Roussigne, M., Kossida, S., Lavigne, A.-C., Clouaire, T., Ecochard, V., Glories, A., Amalric, F., Girard, J.-P. The THAP domain: a novel protein motif with similarity to the DNA-binding domain of P element transposase. Trends Biochem. Sci. 28: 66-69, 2003. [PubMed: 12575992] [Full Text: https://doi.org/10.1016/S0968-0004(02)00013-0]