Section 13: Key Connections for Essays

How does transcription factor binding connect to disease?

Mutations in TFs can alter their DNA-binding domains or motif recognition, preventing them from correctly regulating development, leading to diseases like aniridia (PAX6), synpolydactyly (HOXD13), and various cancers.

How does master TF research connect to iPSCs?

The discovery that master TFs (MyoD, PAX6) can change cell fate inspired Yamanaka to search for TFs that could revert adult cells to pluripotency, leading to iPSCs with Oct4, Sox2, Klf4, and c-Myc.

How do HOX genes demonstrate the importance of spatial and temporal TF control?

HOX genes show that both where (spatial, e.g., anterior-posterior axis) and when (temporal, e.g., timing of activation for digit formation) a TF is expressed determines correct development.

What is the connection between intrinsically disordered regions and disease?

Repeat expansions in intrinsically disordered regions of TFs (like HOXD13) can cause protein aggregation (condensates), preventing normal transcriptional activation and causing developmental diseases