Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

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

ACCESS DATA

Publications

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

Similar Datasets

Project description:Background: Banana (Musa) is one of the most important crops grown in tropical and sub-tropical areas. Cavendish, the most widely grown banana cultivar, is a triploid derived from an intra-species cross. Cavendish is relatively resistant to Race 1 of Fusarium oxysporum f. sp. Cubense (Foc1) which caused wide spread Panama disease during 1960s but is susceptible to Race 4 of Foc (Foc4) which has been causing epidemics in large areas of banana fields in Asia and Australia in the last decade and is threatening world banana production. The genome of the diploid species Musa acuminata (AA) which is the ancestor of a majority of cultivated banana has recently been sequenced. Availability of banana transcriptomes will be highly useful for improving banana genome annotation and assembly and for banana biological research. The knowledge of global gene expression patterns influenced by infection by different Foc races will help to understand the pathogenesis processes and the host responses to the infection. Results: RNA samples extracted from different organs of the Cavendish cultivar were pooled for deep sequencing using the Illumina sequencing technology. The assembled reads were aligned with the genome of M. accuminata and with sequences in the Genbank databases. The analysis led to identification of 842 genes that were not annotated by the Musa genome project. A large number of simple nucleotide polymorphisms (SNPs) and short insertions and deletion (indels) were identified from the transcriptome data. GFP-expressing Foc1 and Foc4 was generated and used to monitor the infection process. Digital gene expression (DGE) profiling analysis was carried out to obtain transcriptome profiles influenced by infection with Foc1 and Foc4 in banana roots at 3, 27, and 51 hours post-inoculation. Both Foc1 and Foc4 were found to be able to invade banana roots and spread to root vascular tissues in the first two days following inoculation. The profiling analysis revealed that inoculation with Foc1 and Foc4 caused similar changes in the gene expression profiles in the infected banana roots. The Foc infection led to induction of many well-known defense-related genes including PATHOGENESIS-RELATED 5 (PR5), PAL, and a lignin-forming peroxidase. The WRKY40 gene, which is a negative regulator of the defense pathway in Arabidopsis, was quickly and strongly suppressed by the infection. Two genes encoding the ethylene biosynthetic enzyme ACC oxidase and several ethylene-responsive transcription factors were among strongly induced genes by both Foc1 and Foc4 Conclusions: Both Foc1 and Foc4 are able to spread into the vascular system of banana roots during the first two days of the infection process and their infection led to similar gene expression profiles in banana roots. The transcriptome profiling analysis indicates that the ethylene synthetic and signalling pathways were activated in response to the Foc infection. Digital gene expression (DGE) profiling analysis was carried out to obtain transcriptome profiles influenced by infection with Foc1 and Foc4 in banana roots at 3, 27, and 51 hours post-inoculation. The plants whose roots were immersed in the culture medium without the pathogen (mock inoculation) were used as a control.

Project description:RNA sequences are expected to be identical to their corresponding DNA sequences. Advances in technologies have enabled deep sequencing of nucleic acids that uncovered exceptions to the one-to-one relationship between DNA and RNA sequences. Previously in human cells, post-transcriptional RNA editing was the only known mechanism that changes RNA sequences from the underlying DNA sequences. Here, we sequenced nascent RNA and found all 12 types of RNA-DNA differences. Using various experimental analyses, we validated this finding. Our results showed that sequences of nascent RNAs within 40 nucleotides of the exit channel of RNA polymerase II already differ from the corresponding DNA sequences. These RNA-DNA differences are mediated by RNA processing steps closely coupled with transcription and not by known deaminase-mediated RNA editing mechanisms nor during NTP incorporation by Pol II. This finding identifies sequence substitution as part of co-transcriptional RNA processing. We sequenced nascent RNA using global run-on sequencing, GRO-seq from human B-cells from two individuals and a variant of the GRO-seq procedure, known as precision run-on sequencing, PRO-seq. The RNAs are prepared after a short run-on assay performed with isolated nuclei in the presence of Br-UTP. The isolated RNAs are base hydrolyzed to ~100 nucleotides and affinity purified with anti-BrU beads three times at each successive step of preparing the RNAs for orientation-specific sequencing using Illumina technology. The 5M-bM-^@M-^Y ~half of each sequence represents nascent RNA made in the cell and the 3M-bM-^@M-^Y ~half represents sequences made in vitro during the run-on reaction. The precision variation, PRO-seq, incorporates one or at most a few biotin-labeled nucleoside triphosphates during the run-on, and sequencing from the 3M-bM-^@M-^Y end of this affinity purified, nascent RNA maps the cellular location of engaged polymerases with near single nucleotide precision. We obtained ~ 100 million 100-nucleotide uniquely mapped GRO-seq reads from B-cells of two individuals. For one subject, we also carried out pGRO-seq and obtained 60 million uniquely mapped reads. In addition, we sequenced ~135 million uniquely mapped RNA-seq reads, and the corresponding DNA of the two individuals to 30X and 60X coverage. Additionally, we isolated and sequenced nascent RNA with an alternate method described by Wuarin and Schibler (1994) in order to compare chromatin-bound RNA to the very nascent RNA from PRO-seq. We obtained ~190 million uniquely mapped reads from chormatin-bound RNA-seq.

Dataset Information

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.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets