Transcriptional repressor [Neurosurgery Wiki]

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====== Transcriptional repressor ======


Transcriptional repressors are usually viewed as [[protein]]s that bind to [[promoter]]s in a way that impedes subsequent binding of [[RNA polymerase]]. Although this repression mechanism is found at several promoters, there is a growing list of repressors that inhibit [[transcription]] initiation in other ways.
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Transcriptional repressors can be classified based on mechanism of action, molecular structure, or biological function. Here's a comprehensive classification:

🔹 By Mechanism of Action
Direct DNA-binding repressors
Bind directly to DNA sequences (usually at promoters or enhancers) to block transcription factor binding or RNA polymerase recruitment.

Example: REST (RE1-Silencing Transcription factor)

Corepressor-dependent repressors
Do not block transcription on their own but recruit corepressors that modify chromatin or inhibit transcription machinery.

Example: NCoR (Nuclear receptor corepressor)

Quenching repressors
Bind to and inactivate transcriptional activators, preventing them from activating gene expression.

Example: Some Groucho/TLE family members

Chromatin-modifying repressors
Recruit enzymes (e.g., histone deacetylases, methyltransferases) that compact chromatin, making DNA inaccessible.

Example: Polycomb group proteins (e.g., EZH2)

Transcriptional interference repressors
Inhibit transcription by transcriptional collision or occlusion, often in bidirectional or overlapping gene regions.

🔹 By Molecular Type or Family
Zinc finger repressors
Contain zinc finger motifs for DNA binding.

Example: Krüppel-like repressors

Homeodomain repressors
Involved in development; often repress genes that specify alternate cell fates.

Example: Engrailed, Hox proteins

Basic helix-loop-helix (bHLH) repressors
Compete with activators or form inactive heterodimers.

Example: Id proteins

Nuclear hormone receptor repressors
Bind to hormone response elements in the absence of ligand and recruit corepressors.

Example: Thyroid hormone receptor (TR) in absence of T3

Polycomb group proteins
Maintain transcriptional repression via chromatin modification over many cell divisions.

Example: PRC1 and PRC2 complexes

🔹 By Biological Role or Context
Developmental repressors
Temporally and spatially regulate gene expression during embryogenesis.

Example: Snail (in epithelial-mesenchymal transition)

Tumor suppressor repressors
Repress genes that promote cell cycle progression or inhibit apoptosis.

Example: Rb protein (retinoblastoma protein)

Epigenetic repressors
Establish heritable transcriptional silencing via DNA methylation and histone modification.

Example: MeCP2
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Zhang et al crucially identified that [[KIF4A]] drives [[glioma]] [[growth]] by [[Rac1]]/[[Cdc42]] [[transcriptional repressor]]s to induce [[cytoskeletal remodeling]] in [[glioma cell]]s. [[Knockdown]] of KIF4A decreased [[RohA]], [[Rac1]], [[Cdc42]], [[Pak1]] and [[Pak2]] expression level. The study provided a prospect that KIF4A functions as an [[oncogene]] in glioma
((Zhang H, Meng S, Chu K, Chu S, Fan YC, Bai J, Yu ZQ. KIF4A drives glioma growth by transcriptional repression of Rac1/Cdc42 to induce cytoskeletal remodeling in glioma cells. J Cancer. 2022 Nov 21;13(15):3640-3651. doi: 10.7150/jca.77238. PMID: 36606197; PMCID: PMC9809311.)).