Talin 1 (TLN1) is best known for its role at focal adhesions, where it activates β-integrin
receptors and transmits mechanical stimuli to the actin cytoskeleton. Interestingly, the
localization of TLN1 is not restricted to the focal adhesions, but its function in other cellular
compartments remains poorly understood. By utilizing both biochemical and confocal
microscopy analyses, we show that TLN1 localizes to the nucleus and that it strongly
interacts with the chromatin. Importantly, depletion of endogenous TLN1 results in extensive
changes in the gene expression profile of human breast epithelial cells. To determine the
impact of nuclear TLN1 on gene regulation, we expressed a TLN1 fusion protein containing
a nuclear localization signal. Our results reve aled that nuclear TLN1 regulates a specific
subset of the TLN1-dependent genes. Taken together, we show that apart from localizing at
the plasma membrane and cytoplasm, TLN1 also resides in the nucleus where it functions in
the regulation of gene expression