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| Status |
Public on Dec 21, 2017 |
| Title |
Binding of High Mobility Group A proteins to the mammalian genome occurs as a function of AT-content [RNA-Seq] |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
High mobility group (HMG) proteins are of similar size as histones with HMGA1 and HMGA2 being particularly abundant in replicating normal tissues and in cancerous cells. While numerous roles for HMGA proteins have been proposed we lack a comprehensive description of their genomic location as a function of chromatin, DNA sequence and functional domains. Here we report such a characterization of HMGA proteins in mouse embryonic stem cells in which we introduce biotin-tagged constructs of wild-type and DNA binding domain mutants. Comparative analysis of their genome-wide distribution reveals pervasive binding, a feature that critically depends on a functional DNA binding domain and which is shared by both HMGA proteins. Assessment of the underlying queues instructive for this binding modality identifies AT richness as the major criteria for local binding. Additionally, we show that other chromatin states such as those linked to cis-regulatory regions have little impact on HMGA binding both in stem and differentiated cells. As a consequence HMGA proteins are found most enriched at regions of higher AT density such as constitutively heterochromatic regions but are absent from enhancers and promoters arguing for a limited role in regulating individual genes. In line with this model we show that genetic deletion of HMGA proteins in stem cells causes limited transcriptional effects and that binding is conserved in neuronal progenitors.
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| Overall design |
RNA-seq was performed in WT, Hmga1 KO and Hmga1/2 add-back mouse embryonic stem cells.
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| Contributor(s) |
Colombo DF, Burger L, Baubec T, Schübeler D |
| Citation(s) |
29267285 |
| |
| Submission date |
Jun 23, 2017 |
| Last update date |
May 15, 2019 |
| Contact name |
Dirk Schuebeler |
| Organization name |
Friedrich Miescher Institute for Biomedical Research
|
| Street address |
Maulbeerstrasse 66
|
| City |
Basel |
| ZIP/Postal code |
4058 |
| Country |
Switzerland |
| |
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| Platforms (1) |
| GPL17021 |
Illumina HiSeq 2500 (Mus musculus) |
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| Samples (15)
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| This SubSeries is part of SuperSeries: |
| GSE100407 |
Binding of High Mobility Group A proteins to the mammalian genome occurs as a function of AT-content |
|
| Relations |
| BioProject |
PRJNA391579 |
| SRA |
SRP110243 |
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