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| Status |
Public on Jan 21, 2020 |
| Title |
CDK-Mediator and FBXL19 cooperate in the induction of developmental genes by promoting regulatory interactions [ChIP-seq] |
| Organisms |
Drosophila melanogaster; Mus musculus |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
Appropriate developmental gene regulation relies on the capacity of gene promoters to integrate inputs from distal regulatory elements, yet how this is achieved remains poorly understood. In embryonic stem cells (ESCs), a subset of silent developmental gene promoters are primed for activation by FBXL19, a CpG island binding protein, through its capacity to recruit CDK-Mediator. How mechanistically these proteins function together to prime genes for activation during differentiation is unknown. Here we discover that in mouse ESCs FBXL19 and CDK-Mediator support long-range interactions between silent gene promoters that rely on FBXL19 for their induction during differentiation and gene regulatory elements. During gene induction, these distal regulatory elements behave in an atypical manner, in that the majority do not acquire histone H3 lysine 27 acetylation and no longer interact with their target gene promoter following gene activation. Despite these atypical features, we demonstrate by targeted deletions that these distal elements are required for appropriate gene induction during differentiation. Together these discoveries demonstrate that CpG-island associated gene promoters can prime genes for activation by communicating with atypical distal gene regulatory elements to achieve appropriate gene expression.
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| Overall design |
Mouse embryonic stem cells in which the CxxC domain of Fbxl19 can be conditionally ablated (Dimitrova et al., eLIFE 290018), were profiled for H3K27ac using spike-in calibrated native ChIP-seq before or after retinoic acid-mediated differentiation
Please note that each *merged_2replicates.bam.bw file was generated from both replicates and is linked to the corresponding rep1 sample records.
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| Contributor(s) |
Feldmann A, Dimitrova E, Kenney A, Klose RJ |
| Citation(s) |
31996894 |
| |
| Submission date |
Aug 27, 2019 |
| Last update date |
Apr 07, 2020 |
| Contact name |
Angelika Feldmann |
| E-mail(s) |
angifeldmann@gmail.com
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| Phone |
7983705260
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| Organization name |
University of Oxford, Department of Biochemistry
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| Street address |
South Parks Road
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| City |
Oxford |
| State/province |
England |
| ZIP/Postal code |
OX1 3QU |
| Country |
United Kingdom |
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| Platforms (1) |
| GPL25537 |
Illumina NextSeq 500 (Drosophila melanogaster; Mus musculus) |
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| Samples (16)
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| This SubSeries is part of SuperSeries: |
| GSE136424 |
CDK-Mediator and FBXL19 cooperate in the induction of developmental genes by promoting regulatory interactions |
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| Relations |
| BioProject |
PRJNA562780 |
| SRA |
SRP219713 |
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