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Joint sequence and chromatin neural networks characterize the differential abilities of Forkhead transcription factors to engage inaccessible chromatin

ABSTRACT: Joint sequence and chromatin neural networks characterize the differential abilities of Forkhead transcription factors to engage inaccessible chromatin

PROVIDER: PRJNA1022802 | ENA |

REPOSITORIES: ENA

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Joint sequence and chromatin neural networks characterize the differential abilities of Forkhead transcription factors to engage inaccessible chromatin (ChIP-exo)

Project description: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.

2023-10-04 | GSE244410 | GEO

Joint sequence and chromatin neural networks characterize the differential abilities of Forkhead transcription factors to engage inaccessible chromatin (ATAC-seq)

2023-10-04 | GSE244409 | GEO

Joint sequence and chromatin neural networks characterize the differential abilities of Forkhead transcription factors to engage inaccessible chromatin (RNA-seq)

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Joint sequence and chromatin neural networks characterize the differential abilities of Forkhead transcription factors to engage inaccessible chromatin (ATAC-seq)

Project description:Joint sequence and chromatin neural networks characterize the differential abilities of Forkhead transcription factors to engage inaccessible chromatin (ATAC-seq)

| PRJNA1022805 | ENA

Joint sequence and chromatin neural networks characterize the differential abilities of Forkhead transcription factors to engage inaccessible chromatin (ChIP-exo)

Project description:Joint sequence and chromatin neural networks characterize the differential abilities of Forkhead transcription factors to engage inaccessible chromatin (ChIP-exo)

| PRJNA1022808 | ENA

Joint sequence and chromatin neural networks characterize the differential abilities of Forkhead transcription factors to engage inaccessible chromatin (RNA-seq)

Project description:Joint sequence and chromatin neural networks characterize the differential abilities of Forkhead transcription factors to engage inaccessible chromatin (RNA-seq)

| PRJNA1022806 | ENA

Diversification of posterior Hox patterning by graded ability to engage inaccessible chromatin

Project description:Diversification of posterior Hox patterning by graded ability to engage inaccessible chromatin

| PRJNA596775 | ENA

Diversification of posterior Hox patterning by graded ability to engage inaccessible chromatin [ATAC-seq]

Project description:While Hox genes encode for similar transcription factors (TFs), they induce different fates across body axes. We sought to understand how Hox TF genomic binding preferences relate to their patterning activities during neuronal differentiation. To generate the required neuronal diversity for locomotor activity, Hox TFs specify spinal motor neuron and interneuron subtypes along the rostro-caudal axis. Our data revelated that Hoxc6 and Hoxc8 of the central group induce limb-innervating fates by binding to the same sites. On the other hand, the posterior group Hox genes assign different positional identities: Hoxc9 (thoracic), Hoxc10 (limb-innervating) and Hox13 (axial elongation termination) by binding to distinct sites with the same primary motif. We find that their genomic binding distributions are explained by differential abilities to bind to previously inaccessible chromatin. Thus, the vertebrate posterior Hox expansion and its associated patterning diversification is the product of their differential abilities to associate with less accessible chromatin.

2020-09-06 | GSE142375 | GEO

Diversification of posterior Hox patterning by graded ability to engage inaccessible chromatin [RNA-seq]

2020-09-06 | GSE142378 | GEO

Diversification of posterior Hox patterning by graded ability to engage inaccessible chromatin [ChIP-seq]

2020-09-06 | GSE142377 | GEO