|
| Status |
Public on Mar 13, 2020 |
| Title |
Evolutionary conserved NSL complex/BRD4 axis controls transcription activation via histone acetylation |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
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.
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| |
|
| Overall design |
Compartive expression analysis of Koolen-de-Vries patient and healthy control fibroblast cell lines
|
| |
|
| Contributor(s) |
Gaub A, Akhtar A |
| Citation(s) |
32382029, 37399316 |
| Submission date |
Aug 13, 2019 |
| Last update date |
Sep 11, 2023 |
| Contact name |
Asifa Akhtar |
| E-mail(s) |
akhtarlab_data@ie-freiburg.mpg.de
|
| Organization name |
Max Planck Institute of Immunobiology and Epigenetics
|
| Department |
Chromatin Regulation
|
| Lab |
Akhtar Lab
|
| Street address |
Stuebeweg 51
|
| City |
Freiburg |
| ZIP/Postal code |
79108 |
| Country |
Germany |
| |
|
| Platforms (1) |
| GPL21290 |
Illumina HiSeq 3000 (Homo sapiens) |
|
| Samples (7)
|
| GSM4029679 |
human_fibroblast_PolyA_RNAseq_KdV_patient1 |
| GSM4029680 |
human_fibroblast_PolyA_RNAseq_KdV_patient2 |
| GSM4029681 |
human_fibroblast_PolyA_RNAseq_KdV_patient3 |
| GSM4029682 |
human_fibroblast_PolyA_RNAseq_KdV_healthy_control1 |
| GSM4029683 |
human_fibroblast_PolyA_RNAseq_KdV_healthy_control2 |
| GSM4029684 |
human_fibroblast_PolyA_RNAseq_KdV_healthy_control3 |
| GSM4029685 |
human_fibroblast_PolyA_RNAseq_KdV_healthy_control4 |
|
| This SubSeries is part of SuperSeries: |
| GSE135815 |
Evolutionary conserved NSL complex/BRD4 axis controls transcription activation via histone acetylation |
|
| Relations |
| BioProject |
PRJNA560038 |
| SRA |
SRP218226 |
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