PLX078895

GSE135773: Evolutionary conserved NSL complex/BRD4 axis controls transcription activation via histone acetylation

• Organsim human
• Type RNASEQ
• Target gene
• Project ARCHS4

Cells rely on a diverse repertoire of genes for maintaining homeostasis, but the transcriptional networks underlying their expression remain poorly understood. The MOF acetyltransferase-containing Non-Specific Lethal (NSL) complex is a broad transcription regulator. It is essential in Drosophila and haploinsufficiency of the human KANSL1 subunit results in the Koolen-de Vries syndrome. Here, we perform a genome-wide RNAi screen and identify the BET protein BRD4 as evolutionary conserved co-factor of the NSL complex. Using Drosophila and mouse embryonic stem cells, we characterise a recruitment hierarchy, where NSL-deposited histone acetylation induces BRD4 recruitment for transcription of constitutively active genes. Transcriptome analyses in Koolen-de Vries patient-derived fibroblasts reveals perturbations with a cellular homeostasis signature that are evoked by the NSL complex/BRD4-axis. We propose that BRD4 represents a conserved bridge between the NSL complex and transcription activation and provide a new perspective in the understanding of their functions in healthy and diseased states. SOURCE: Asifa Akhtar (akhtarlab_data@ie-freiburg.mpg.de) - Akhtar Lab Max Planck Institute of Immunobiology and Epigenetics