Lap2α is required for MRTF-A-SRF transcriptional activity [RNA-seq]

Myocardin-related transcription factor A (MRTF-A) in complex with the serum response factor (SRF) regulates the expression of cytoskeletal genes in response to cytoplasmic and nuclear actin dynamics. Different components of nucleoskeleton, besides nuclear actin, also regulate the activity of MRTF-A. Here we extend these studies by showing that lamina-associated polypeptide 2α (Lap2α), the nucleoplasmic isoform of Lap2, is a novel regulator, and a direct binding partner of MRTF-A. Lap2α is a nucleoplasmic protein that interacts with A-type lamins and the retinoblastoma protein (pRb) and contributes to chromatin organization. Unlike other known MRTF-A regulators, Lap2α is not required for MRTF-A nucleo-cytoplasmic shuttling; it functions within the nucleus where it binds MRTF-A directly via its unique C-terminal domain prior to MRTF-A forming the complex with chromatin and SRF. Such interaction affects MRTF-A transcriptional activity since genome-wide analysis revealed reduced binding of MRTF-A to SRF target genes in Lap2α  knockout cells compared to control cells that consequently led to impaired expression of target genes. Our studies therefore add another regulatory layer to the control MRTF-A-SRF-mediated gene expression, and broaden the role of Lap2α in transcriptional regulation. To investigate the effect of Lap2 knockdown on gene expression, we performed RNA sequencing (RNA-seq) analysis of control and Lap2-depleted cells cultivated in serum-starved (0.3% FBS) conditions and after 45 min of serum stimulation (15% FBS) in triplicates.