DUX4

3D Model

DUX4 is a critical transcription factor unique to eutherian mammals, crucial in embryogenesis regulation and linked to diseases such as FSHD and B cell leukemia. Its evolutionary journey involved the duplication of a single ancestral homeobox into two, creating tandem homeodomains, HD1 and HD2, connected by a linker region. This structure allows DUX4 to recognize specific DNA sequences crucial for gene regulation, with HD1 targeting the 5’-TAAT-3’ sequence and HD2 binding to the 5’-TGAT-3’. The presence of a primate-specific salt bridge between Glu70 and Arg73 in HD1 underscores its evolutionary adaptation and specificity in gene regulation.the head-to-head orientation of HD1 and HD2, facilitated by the linker region and their ability to recognize different DNA sequences. This interaction, characterized by dynamic positioning and electrostatic interactions,is key to understanding DUX4’s function and targeting therapies.

More details are displayed in the 3D image.

HD1=pink HD2=yellow