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Transcription Factor-Directed Re-wiring of Chromatin Architecture for Somatic Cell Nuclear Reprogramming toward trans-Differentiation.

Publication ,  Journal Article
Dall'Agnese, A; Caputo, L; Nicoletti, C; di Iulio, J; Schmitt, A; Gatto, S; Diao, Y; Ye, Z; Forcato, M; Perera, R; Bicciato, S; Telenti, A ...
Published in: Mol Cell
November 7, 2019

MYOD-directed fibroblast trans-differentiation into skeletal muscle provides a unique model to investigate how one transcription factor (TF) reconfigures the three-dimensional chromatin architecture to control gene expression, which is otherwise achieved by the combinatorial activities of multiple TFs. Integrative analysis of genome-wide high-resolution chromatin interactions, MYOD and CTCF DNA-binding profile, and gene expression, revealed that MYOD directs extensive re-wiring of interactions involving cis-regulatory and structural genomic elements, including promoters, enhancers, and insulated neighborhoods (INs). Re-configured INs were hot-spots of differential interactions, whereby MYOD binding to highly constrained sequences at IN boundaries and/or inside INs led to alterations of promoter-enhancer interactions to repress cell-of-origin genes and to activate muscle-specific genes. Functional evidence shows that MYOD-directed re-configuration of chromatin interactions temporally preceded the effect on gene expression and was mediated by direct MYOD-DNA binding. These data illustrate a model whereby a single TF alters multi-loop hubs to drive somatic cell trans-differentiation.

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Published In

Mol Cell

DOI

EISSN

1097-4164

Publication Date

November 7, 2019

Volume

76

Issue

3

Start / End Page

453 / 472.e8

Location

United States

Related Subject Headings

  • Transcription, Genetic
  • Structure-Activity Relationship
  • Protein Binding
  • Phenotype
  • Nucleic Acid Conformation
  • Myoblasts, Skeletal
  • MyoD Protein
  • Muscle Development
  • Mice
  • Humans
 

Citation

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Dall’Agnese, A., Caputo, L., Nicoletti, C., di Iulio, J., Schmitt, A., Gatto, S., … Puri, P. L. (2019). Transcription Factor-Directed Re-wiring of Chromatin Architecture for Somatic Cell Nuclear Reprogramming toward trans-Differentiation. Mol Cell, 76(3), 453-472.e8. https://doi.org/10.1016/j.molcel.2019.07.036
Dall’Agnese, Alessandra, Luca Caputo, Chiara Nicoletti, Julia di Iulio, Anthony Schmitt, Sole Gatto, Yarui Diao, et al. “Transcription Factor-Directed Re-wiring of Chromatin Architecture for Somatic Cell Nuclear Reprogramming toward trans-Differentiation.Mol Cell 76, no. 3 (November 7, 2019): 453-472.e8. https://doi.org/10.1016/j.molcel.2019.07.036.
Dall’Agnese A, Caputo L, Nicoletti C, di Iulio J, Schmitt A, Gatto S, et al. Transcription Factor-Directed Re-wiring of Chromatin Architecture for Somatic Cell Nuclear Reprogramming toward trans-Differentiation. Mol Cell. 2019 Nov 7;76(3):453-472.e8.
Dall’Agnese, Alessandra, et al. “Transcription Factor-Directed Re-wiring of Chromatin Architecture for Somatic Cell Nuclear Reprogramming toward trans-Differentiation.Mol Cell, vol. 76, no. 3, Nov. 2019, pp. 453-472.e8. Pubmed, doi:10.1016/j.molcel.2019.07.036.
Dall’Agnese A, Caputo L, Nicoletti C, di Iulio J, Schmitt A, Gatto S, Diao Y, Ye Z, Forcato M, Perera R, Bicciato S, Telenti A, Ren B, Puri PL. Transcription Factor-Directed Re-wiring of Chromatin Architecture for Somatic Cell Nuclear Reprogramming toward trans-Differentiation. Mol Cell. 2019 Nov 7;76(3):453-472.e8.
Journal cover image

Published In

Mol Cell

DOI

EISSN

1097-4164

Publication Date

November 7, 2019

Volume

76

Issue

3

Start / End Page

453 / 472.e8

Location

United States

Related Subject Headings

  • Transcription, Genetic
  • Structure-Activity Relationship
  • Protein Binding
  • Phenotype
  • Nucleic Acid Conformation
  • Myoblasts, Skeletal
  • MyoD Protein
  • Muscle Development
  • Mice
  • Humans