THAP7 (THAP Domain Containing 7) is a chromatin-associated protein encoded by the THAP7 gene in humans. It plays a critical role in transcriptional repression through interactions with histones and corepressor complexes. This protein is implicated in cellular processes such as cell cycle regulation and epigenetic control, with emerging evidence linking it to cancer progression and developmental disorders .
Identifier Type | Value |
---|---|
HGNC ID | 23190 |
NCBI Gene ID | 80764 |
Ensembl ID | ENSG00000184436 |
UniProt Accession | Q9BT49 |
OMIM® ID | 609518 |
The THAP7 gene is located on human chromosome 22 and encodes a 309-amino acid protein .
THAP7 binds hypoacetylated histone H4 tails and recruits histone deacetylase 3 (HDAC3) and nuclear receptor corepressors (NCoR) to repress transcription .
THAP7 represses gene expression by:
Recruiting HDAC3 and NCoR: These complexes deacetylate histones, leading to chromatin condensation and transcriptional silencing .
Targeting Hypoacetylated Histones: Binds un-, mono-, and diacetylated histone H4 tails, acting as a signal transducer for repressive chromatin marks .
Inhibiting p21 Expression: Reduces acetylation of histone H3 on the p21 promoter, suppressing cell cycle arrest in lung adenocarcinoma (LUAD) .
THAP7 promotes G1/S phase transition by:
Accelerating DNA Replication: Overexpression in LUAD cells increases S-phase progression .
Modulating E2F Targets: Regulates RRM1 expression via THAP1/THAP3-HCFC1-OGT complexes .
Disease | Role of THAP7 | Evidence Source |
---|---|---|
Bladder Exstrophy | Genetic risk factor | GeneCards |
Lung Adenocarcinoma | Tumor promoter; poor prognosis | PMC |
Cardiovascular Diseases | Dysregulation linked to pathogenesis | Abcam |
THAP7 may serve as a target for:
Epigenetic Therapies: Inhibiting HDAC3 recruitment to block histone deacetylation.
Biomarker Development: Detecting elevated THAP7 levels in LUAD for prognosis .
Protein Partner | Interaction Score | Function |
---|---|---|
HDAC3 | 0.673 | Histone deacetylation |
NCOR1 | 0.760 | Corepressor complex formation |
H4C6 (Histone H4) | 0.816 | Chromatin binding |
THAP7 is a chromatin-associated protein that binds to histone tails and represses transcription by recruiting histone deacetylase 3 (HDAC3) and nuclear hormone receptor corepressors . The human recombinant form of THAP7 is produced in Escherichia coli and is a single, non-glycosylated polypeptide chain containing 332 amino acids, with a molecular mass of approximately 36.8 kDa . It includes a 23 amino acid His-tag at the N-terminus, which facilitates its purification through chromatographic techniques .
THAP7 is involved in the repression of transcription by interacting with other proteins and chromatin components. It associates with template-activating factor-Iβ (TAF-Iβ), also known as PHAPII, SET, and I2PP2A, which is a component of the inhibitor of acetyltransferases (INHAT) complex . This complex masks histone acetylation and blocks histone acetyltransferase (HAT)-dependent transcription, thereby maintaining histones in a hypoacetylated, repressed state .
THAP7 also interacts with histone H3 and histone H4, inhibiting their acetylation . This interaction is crucial for its role in transcriptional repression, as acetylation of histones is generally associated with transcriptional activation. By preventing histone acetylation, THAP7 helps to maintain a repressed chromatin state, thereby regulating gene expression.
The regulation of chromatin structure and histone modifications is critical for the control of gene expression. THAP7, through its interactions with histones and other chromatin-associated proteins, plays a vital role in this process. Its ability to recruit corepressors and inhibit histone acetylation highlights its importance in maintaining the balance between transcriptional activation and repression.