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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Oct 04, 2023 |
| Title |
Joint sequence and chromatin neural networks characterize the differential abilities of Forkhead transcription factors to engage inaccessible chromatin (ATAC-seq) |
| Organism |
Mus musculus |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
The DNA-binding activities of transcription factors (TFs) are influenced by both intrinsic sequence preferences and extrinsic interactions with cell-specific chromatin landscapes and other regulatory proteins. Disentangling the roles of these determinants in TF-DNA binding remains challenging. For instance, the FoxA subfamily of Forkhead domain TFs are known pioneer factors, yet their binding varies across cell types, pointing to a combination of intrinsic and extrinsic forces guiding their binding. How such sequence and chromatin influences vary across related Forkhead domain TFs remains mostly uncharacterized. Here, we present a principled approach to compare the relative contributions of intrinsic DNA sequence preference and cell-specific chromatin environments to a TF’s DNA-binding activities. We over-express a selection of Fox TFs in mouse embryonic stem (mES) cells, which offer a platform to contrast each TF's binding activity within the same preexisting chromatin background. By developing and applying a neural network that jointly models sequence and chromatin data, we can evaluate how sequence and preexisting chromatin features contribute to induced TF binding, both at individual sites and genome-wide. We demonstrate that Fox TFs bind different DNA targets, and drive differential gene expression patterns, even when induced in identical chromatin settings. Differential Fox binding activities can be attributed to distinct DNA-binding preferences coupled with differential abilities to engage relatively inaccessible chromatin. We propose that varying preferences for preexisting chromatin states enables the functional diversification of paralogous TFs.
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| Overall design |
Genome-wide ATAC-seq profiling of chromatin accessibility after over-expression of selected Forkhead domain transcription factors in mouse embryonic stem cells
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| Contributor(s) |
Arora S, Yang J, Akiyama T, James D, Morrissey A, Blanda TR, Badjatia N, Lai WK, Ko MS, Pugh BF, Mahony S |
| Citation missing |
Has this study been published? Please login to update or notify GEO. |
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| Submission date |
Sep 30, 2023 |
| Last update date |
Oct 04, 2023 |
| Contact name |
Shaun Mahony |
| E-mail(s) |
mahony@psu.edu
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| Phone |
814-865-3008
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| Organization name |
Penn State University
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| Department |
Biochemistry & Molecular Biology
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| Lab |
Shaun Mahony
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| Street address |
404 South Frear Bldg
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| City |
University Park |
| State/province |
PA |
| ZIP/Postal code |
16802 |
| Country |
USA |
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| Platforms (1) |
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| Samples (12)
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| GSM7815560 |
iFoxA1, mES+24hrs, ATAC-seq, rep2 |
| GSM7815561 |
iFoxC1, mES+24hrs, ATAC-seq, rep1 |
| GSM7815562 |
iFoxC1, mES+24hrs, ATAC-seq, rep2 |
| GSM7815563 |
iFoxG1, mES+24hrs, ATAC-seq, rep1 |
| GSM7815564 |
iFoxG1, mES+24hrs, ATAC-seq, rep2 |
| GSM7815565 |
iFoxL2, mES+24hrs, ATAC-seq, rep1 |
| GSM7815566 |
iFoxL2, mES+24hrs, ATAC-seq, rep2 |
| GSM7815567 |
iFoxP3, mES+24hrs, ATAC-seq, rep1 |
| GSM7815568 |
iFoxP3, mES+24hrs, ATAC-seq, rep2 |
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| This SubSeries is part of SuperSeries: |
| GSE244411 |
Joint sequence and chromatin neural networks characterize the differential abilities of Forkhead transcription factors to engage inaccessible chromatin |
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| Relations |
| BioProject |
PRJNA1022805 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE244409_RAW.tar |
664.2 Mb |
(http)(custom) |
TAR (of BW) |
SRA Run Selector |
| Raw data are available in SRA |
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