Coupling myosin to gene expression

Myosin VI is a unique minus-end molecular motor known to interact with various binding partners in many diverse functions. The motor is present in the nucleus and forms interactions with RNA Polymerase II. However, very little is known about the function or interactions in the nucleus.
Utilizing a combination of cell biology, biochemistry and biophysics, we have shown that the C-Terminal domain of myosin VI binds DNA through a mechanism regulated by nuclear co-factor NDP52. NDP52 relieves an auto-inhibited state where myosin VI is back-folded to enable both DNA binding and motor protein dimerization – a process which converts Myosin VI to a processive motor.
To explore how this is related to gene expression, we have used in vitro transcription assays, here depletion of either NDP52 or myosin VI, reduces the steady-state mRNA levels. Moreover, through competition assays we have been able to determine Myosin VI associates to RNAPII through two locations (1) motor domain through actin and (2) its C-Terminal domain through a combination of binding partner and DNA.
Therefore, we present a model whereby myosin VI is recruited to the genome through its binding partner, which activates the protein, enabling DNA binding and dimerization. The complex then associates with RNAPII to drive transcription.