TFs

Transcription factors (TFs) are proteins that regulate gene expression by binding to specific DNA sequences near target genes, typically in promoters or enhancers. By interacting with the transcriptional machinery and other regulatory proteins, TFs can activate or repress transcription in response to developmental cues and environmental signals.

Most TFs have modular structures that include a DNA-binding domain and one or more activation or repression domains. The DNA-binding domain recognizes particular motifs, while the regulatory domain recruits co-factors, chromatin-modifying enzymes, or RNA polymerase II. TFs are organized into families based on shared DNA-binding domains, such as zinc finger, basic leucine zipper (bZIP), basic helix-loop-helix (bHLH), and homeobox domains. They often influence chromatin structure and accessibility, acting in concert with other factors.

Functioning in regulatory networks, TFs respond to signaling pathways and participate in combinatorial control, where multiple TFs determine a gene’s expression level. Some TFs act as pioneer factors, able to bind condensed chromatin and recruit other TFs. TFs can serve as activators, repressors, or context-dependent regulators, and their activity is modulated by post-translational modifications and interactions with co-regulators.

TFs play crucial roles in development, differentiation, metabolism, and stress responses. Dysregulation or mutations in TFs can lead to developmental disorders and cancers. Well-known examples include p53 (tumor suppression), NF-κB (inflammation), OCT4/SOX2 (pluripotency), and GATA1 (erythroid development).

Research methods for TFs include chromatin immunoprecipitation followed by sequencing (ChIP-seq), DNase I footprinting, and various binding assays. These approaches help map TF binding sites and reconstruct gene regulatory networks.