Similar Datasets
Project description:Single-cell multi-scale footprinting reveals the modular organization of DNA regulatory elements
| PRJNA893648 | ENA
Project description:Cis-regulatory elements (CREs) are bound by diverse chromatin-associated proteins, cooperate to establish gene expression, and change in structure over time to alter cell fate and function1–3. Here, we develop a footprinting framework that uses deep learning to correct Tn5 sequence bias, improving accuracy and reducing false positives. This framework additionally identifies the interaction of DNA with objects of various sizes. Using these ‘multi-scale footprints’ we find that transcription factor (TF) binding occurs at well-defined distances from nucleosomes. Further, we demonstrate that multi-scale footprints, which include the positions of nucleosomes, enable more accurate inference of TF binding. Using multi-scale footprinting with single-cell multi-omics, we discover wide-spread structural and functional changes of CREs across hematopoiesis, wherein nucleosomes slide, expose DNA for TF binding, and promote gene expression. Finally, we apply this single-cell and footprint approach to characterize age-associated structural changes to CREs within hematopoietic stem cells and identify a spectrum of cells harboring age-associated changes to the epigenome. Interestingly, we find extensive changes to the structure of CREs upon aging, with many age-associated changes altering CRE structure while preserving overall accessibility. Collectively, we reveal the dynamics and functional importance of CRE structure, highlighting changes to gene regulation at single-cell and single-base-pair resolution.
2023-03-29 | GSE216406 | GEO
Project description:Cis-regulatory elements (CREs) are bound by diverse chromatin-associated proteins, cooperate to establish gene expression, and change in structure over time to alter cell fate and function1–3. Here, we develop a footprinting framework that uses deep learning to correct Tn5 sequence bias, improving accuracy and reducing false positives. This framework additionally identifies the interaction of DNA with objects of various sizes. Using these ‘multi-scale footprints’ we find that transcription factor (TF) binding occurs at well-defined distances from nucleosomes. Further, we demonstrate that multi-scale footprints, which include the positions of nucleosomes, enable more accurate inference of TF binding. Using multi-scale footprinting with single-cell multi-omics, we discover wide-spread structural and functional changes of CREs across hematopoiesis, wherein nucleosomes slide, expose DNA for TF binding, and promote gene expression. Finally, we apply this single-cell and footprint approach to characterize age-associated structural changes to CREs within hematopoietic stem cells and identify a spectrum of cells harboring age-associated changes to the epigenome. Interestingly, we find extensive changes to the structure of CREs upon aging, with many age-associated changes altering CRE structure while preserving overall accessibility. Collectively, we reveal the dynamics and functional importance of CRE structure, highlighting changes to gene regulation at single-cell and single-base-pair resolution.
2023-03-29 | GSE216403 | GEO
Project description:Cis-regulatory elements (CREs) are bound by diverse chromatin-associated proteins, cooperate to establish gene expression, and change in structure over time to alter cell fate and function1–3. Here, we develop a footprinting framework that uses deep learning to correct Tn5 sequence bias, improving accuracy and reducing false positives. This framework additionally identifies the interaction of DNA with objects of various sizes. Using these ‘multi-scale footprints’ we find that transcription factor (TF) binding occurs at well-defined distances from nucleosomes. Further, we demonstrate that multi-scale footprints, which include the positions of nucleosomes, enable more accurate inference of TF binding. Using multi-scale footprinting with single-cell multi-omics, we discover wide-spread structural and functional changes of CREs across hematopoiesis, wherein nucleosomes slide, expose DNA for TF binding, and promote gene expression. Finally, we apply this single-cell and footprint approach to characterize age-associated structural changes to CREs within hematopoietic stem cells and identify a spectrum of cells harboring age-associated changes to the epigenome. Interestingly, we find extensive changes to the structure of CREs upon aging, with many age-associated changes altering CRE structure while preserving overall accessibility. Collectively, we reveal the dynamics and functional importance of CRE structure, highlighting changes to gene regulation at single-cell and single-base-pair resolution.
2023-03-29 | GSE216405 | GEO
Project description:Cis-regulatory elements (CREs) are bound by diverse chromatin-associated proteins, cooperate to establish gene expression, and change in structure over time to alter cell fate and function1–3. Here, we develop a footprinting framework that uses deep learning to correct Tn5 sequence bias, improving accuracy and reducing false positives. This framework additionally identifies the interaction of DNA with objects of various sizes. Using these ‘multi-scale footprints’ we find that transcription factor (TF) binding occurs at well-defined distances from nucleosomes. Further, we demonstrate that multi-scale footprints, which include the positions of nucleosomes, enable more accurate inference of TF binding. Using multi-scale footprinting with single-cell multi-omics, we discover wide-spread structural and functional changes of CREs across hematopoiesis, wherein nucleosomes slide, expose DNA for TF binding, and promote gene expression. Finally, we apply this single-cell and footprint approach to characterize age-associated structural changes to CREs within hematopoietic stem cells and identify a spectrum of cells harboring age-associated changes to the epigenome. Interestingly, we find extensive changes to the structure of CREs upon aging, with many age-associated changes altering CRE structure while preserving overall accessibility. Collectively, we reveal the dynamics and functional importance of CRE structure, highlighting changes to gene regulation at single-cell and single-base-pair resolution.
2023-03-29 | GSE216404 | GEO
Project description:Cis-regulatory elements (CREs) are bound by diverse chromatin-associated proteins, cooperate to establish gene expression, and change in structure over time to alter cell fate and function1–3. Here, we develop a footprinting framework that uses deep learning to correct Tn5 sequence bias, improving accuracy and reducing false positives. This framework additionally identifies the interaction of DNA with objects of various sizes. Using these ‘multi-scale footprints’ we find that transcription factor (TF) binding occurs at well-defined distances from nucleosomes. Further, we demonstrate that multi-scale footprints, which include the positions of nucleosomes, enable more accurate inference of TF binding. Using multi-scale footprinting with single-cell multi-omics, we discover wide-spread structural and functional changes of CREs across hematopoiesis, wherein nucleosomes slide, expose DNA for TF binding, and promote gene expression. Finally, we apply this single-cell and footprint approach to characterize age-associated structural changes to CREs within hematopoietic stem cells and identify a spectrum of cells harboring age-associated changes to the epigenome. Interestingly, we find extensive changes to the structure of CREs upon aging, with many age-associated changes altering CRE structure while preserving overall accessibility. Collectively, we reveal the dynamics and functional importance of CRE structure, highlighting changes to gene regulation at single-cell and single-base-pair resolution.
2023-03-29 | GSE216462 | GEO
Project description:Cis-regulatory elements (CREs) are bound by diverse chromatin-associated proteins, cooperate to establish gene expression, and change in structure over time to alter cell fate and function1–3. Here, we develop a footprinting framework that uses deep learning to correct Tn5 sequence bias, improving accuracy and reducing false positives. This framework additionally identifies the interaction of DNA with objects of various sizes. Using these ‘multi-scale footprints’ we find that transcription factor (TF) binding occurs at well-defined distances from nucleosomes. Further, we demonstrate that multi-scale footprints, which include the positions of nucleosomes, enable more accurate inference of TF binding. Using multi-scale footprinting with single-cell multi-omics, we discover wide-spread structural and functional changes of CREs across hematopoiesis, wherein nucleosomes slide, expose DNA for TF binding, and promote gene expression. Finally, we apply this single-cell and footprint approach to characterize age-associated structural changes to CREs within hematopoietic stem cells and identify a spectrum of cells harboring age-associated changes to the epigenome. Interestingly, we find extensive changes to the structure of CREs upon aging, with many age-associated changes altering CRE structure while preserving overall accessibility. Collectively, we reveal the dynamics and functional importance of CRE structure, highlighting changes to gene regulation at single-cell and single-base-pair resolution.
2023-03-29 | GSE216461 | GEO
Project description:Multi-scale chromatin footprinting reveals wide-spread alterations to the structure of DNA regulatory elements [BAC]
| PRJNA893555 | ENA
Project description:Multi-scale chromatin footprinting reveals wide-spread alterations to the structure of DNA regulatory elements [scATAC]
| PRJNA893558 | ENA
Project description:Regulatory regions harbor multiple transcription factor (TF) recognition sites; however, the contribution of individual sites to regulatory function remains challenging to define. We describe an approach that exploits the error-prone nature of genome editing-induced double-strand break repair to map functional elements within regulatory DNA at nucleotide resolution. We demonstrate the approach on a human erythroid enhancer, revealing single TF recognition sites that gate the majority of downstream regulatory function.
| S-EPMC5381659 | biostudies-literature