Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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Distinct structural transitions of chromatin topological domains coordinate hormone-induced gene regulation

ABSTRACT: The three-dimensional (3D) organization of the genome within the cell nucleus contributes to cell-specific gene expression in different cell types1. High-throughput 3CM-bM-^@M-^Sderived methods have revealed that the genome is segmented into contiguous topologically associating domains (TADs), which help to orchestrate gene expression changes during differentiation and development2-5. Using ChIP-Seq, Hi-C and 3D modelling techniques, we reveal that TADs regulate the rapid gene expression changes induced by progestin in T47D breast cancer cells. In response to the hormone, TADs maintain their borders and operate as discrete regulatory units in which the majority of the genes are either transcriptionally activated or repressed. Additionally, the epigenetic signatures of the TADs are coordinately modified by hormone in correlation with the transcriptional changes. Hormone-induced changes in gene activity and chromatin remodelling are accompanied by structural changes that are distinct for activated or repressed TADs. Integrative 3D modelling revealed that TADs are structurally expanded if active and compacted if repressed, and that this is accompanied by differential changes in accessibility. We thus propose that TADs function as M-bM-^@M-^\regulonsM-bM-^@M-^] to enable spatially proximal genes to be coordinately transcribed in response to hormones. T47D-MTVL human breast cancer cells were incubated with the progestin R5020 for different times at 37M-BM-:C and prepared for ChIP-Seq or Hi-C according published protocols

ORGANISM(S): Homo sapiens

SUBMITTER: Miguel Beato

PROVIDER: E-GEOD-53463 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Distinct structural transitions of chromatin topological domains correlate with coordinated hormone-induced gene regulation.

Le Dily François F Baù Davide D Pohl Andy A Vicent Guillermo P GP Serra François F Soronellas Daniel D Castellano Giancarlo G Wright Roni H G RH Ballare Cecilia C Filion Guillaume G Marti-Renom Marc A MA Beato Miguel M

Genes & development 20141001 19

The human genome is segmented into topologically associating domains (TADs), but the role of this conserved organization during transient changes in gene expression is not known. Here we describe the distribution of progestin-induced chromatin modifications and changes in transcriptional activity over TADs in T47D breast cancer cells. Using ChIP-seq (chromatin immunoprecipitation combined with high-throughput sequencing), Hi-C (chromosome capture followed by high-throughput sequencing), and thre ...[more]

PMID: 25274727

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Distinct structural transitions of chromatin topological domains coordinate hormone-induced gene regulation

Publications

Distinct structural transitions of chromatin topological domains correlate with coordinated hormone-induced gene regulation.

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