We want to understand the mechanisms by which actin operates in the nucleus to regulate essential nuclear events, such as gene expression and maintenance of genomic integrity.
Actin has been linked to processes spanning the whole gene expression cascade, but the molecular mechanisms have remained unclear.
We are using a combination of functional genomics, advanced imaging techniques and biochemistry to understand how actin contributes to gene expression. We are especially interested in the role of actin in transcription by RNA polymerase II, and our studies have shown that actin interacts with virtually all transcribed genes (Sokolova et al. 2018).
We are now dissecting the interactions between actin and the transcription machinery by using biochemical methods. To study the biological relevance of actin for transcription, we use both fruit fly and cultured mammalian and fly cells as model system.
In the cytoplasm, the main function of actin is to provide force for movement. Also in the nucleus, actin has been linked to chromatin movement events, but both the mechanisms and relevance have remained unclear.
To study this, we are using different advanced microscopy methods to study actin and chromatin dynamics in living cells.
In addition to its “general” role in gene expression, actin also regulates the activity of specific transcription factors, such as MRTF-A, which is a transcription cofactor for serum response factor SRF.
Actin dynamics regulates both the subcellular localization of MRTF-A, as well as its nuclear activity (Vartiainen et al. 2007). The mechanisms by which this regulation takes place within the nucleus has remained unclear, however.
We are using a combination of functional genomics, cell biological and biochemical methods to unravel the mechanisms by which nuclear MRTF-A is regulated and to reveal the interplay between actin and MRTF in gene expression.