Transcriptional repressor

Transcriptional repressors are usually viewed as proteins that bind to promoters 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.

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

Zhang et al crucially identified that KIF4A drives glioma growth by Rac1/Cdc42 transcriptional repressors to induce cytoskeletal remodeling in glioma cells. 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 ¹⁾.