Biology subjects

Vartiainen, M.

Publications and source records attributed to Vartiainen, M..

3 recordsLinked to original sources

bioRxiv2021

Lamina-associated polypeptide 2α is required for intranuclear MRTF-A activity

Myocardin-related transcription factor A (MRTF-A), a coactivator of serum response factor (SRF), regulates the expression of many cytoskeletal genes in response to cytoplasmic and nuclear actin dynamics. Here we describe a novel mechanism to regulate MRTF-A activity within the nucleus by showing that lamina-associated polypeptide 2 (Lap2), the nucleoplasmic isoform of Lap2, is a direct binding partner of MRTF-A, and required for the efficient expression of MRTF-A/SRF target genes. Mechanistically, Lap2 is not required for MRTF-A nuclear localization, unlike most other MRTF-A regulators, but is required for binding of MRTF-A to its target genes. This regulatory step takes place prior to MRTF-A chromatin binding, because Lap2 neither interacts with, nor specifically influences active histone marks on MRTF-A/SRF target genes. Phenotypically, Lap2 is required for serum-induced cell migration, and deregulated MRTF-A activity may also contribute to muscle and proliferation phenotypes associated with loss of Lap2. Our studies therefore add another regulatory layer to the control of MRTF-A-SRF-mediated gene expression, and broaden the role of Lap2 in transcriptional regulation.

cell biology↗

bioRxiv2018

Nuclear actin interactome analysis links actin to KAT14 histone acetyl transferase and mRNA splicing

In addition to its essential functions within the cytoskeleton, actin also localizes to the cell nucleus, where it is linked to many important nuclear processes from gene expression to maintenance of genomic integrity. However, the molecular mechanisms by which actin operates in the nucleus remain poorly understood. Here we have used two complementary mass spectrometry (MS) techniques, AP-MS and BioID-MS, to identify binding partners for nuclear actin. Common high-confidence interactions highlight the role of actin in chromatin remodeling complexes and identify the hATAC histone modifier as a novel actin-containing nuclear complex. Further analysis demonstrates that actin binds directly to the hATAC subunit KAT14, and modulates its histone acetyl transferase activity in vitro and in cells. BioID-MS, which can detect also transient interactions, links actin to several steps of transcription as well as to RNA processing. Alterations in nuclear actin levels disturb alternative exon skipping of the SMN2 minigene, suggesting also a functional role for actin in RNA splicing. This interactome analysis thus identifies both novel direct binding partners and functional roles for nuclear actin, as well as forms a platform for further mechanistic studies on how actin operates during essential nuclear processes.

cell biology↗

bioRxiv2018

Nuclear actin is required for transcription during Drosophila oogenesis

Actin influences gene expression at multiple levels. It regulates the activity of specific transcription factors, such as myocardin-related transcription factor (MRTF), is a component of many chromatin remodelers and linked to transcription by all three RNA polymerases (Pol). However, the molecular mechanisms by which actin participates in the gene-specific vs. general transcription have remained unclear. Here we use chromatin immunoprecipitation followed by deep sequencing (ChIP-seq) in Drosophila ovaries to demonstrate that binding of actin to the Act5C gene is not dependent on the Mrtf transcription cofactor. At the genome-wide level, actin interacts with essentially all transcribed genes and co-occupies most gene promoters together with Pol II. On highly expressed genes, actin and Pol II can be found also on the gene bodies. Manipulation of nuclear transport factors for actin leads to decreased expression of egg shell genes, demonstrating the in vivo relevance of balanced nucleo-cytoplasmic shuttling of actin for transcription.

cell biology↗