Transcriptionally active enhancers in human cancer cells
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ABSTRACT:
PROVIDER: PRJNA638913 | ENA |
REPOSITORIES: ENA
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Project description:The growth of human cancer cells is driven by aberrant enhancer and gene transcription activity. Here we use Transient Transcriptome sequencing (TT-seq) to map thousands of transcriptionally active putative enhancers in fourteen human cancer cell lines covering seven cancer types. We conducted an in-depth analysis of the data, derived thousands of putative enhancer-promoter pairs, and extracted general features of active enhancer and transcription landscapes in cancer cells. We provide a comprehensive catalog of transcribed candidate enhancers with cancer-associated somatic mutations and putative enhancer-promoter pairs involving cancer-associated genes. Overall our results serve as a resource to study enhancer activity and gene regulation, and to select candidate enhancers for functional studies.
2021-01-12 | GSE152291 | GEO
Project description: Not available
| S-EPMC7838827 | biostudies-literature
Project description:Primed enhancers are marked by histone H3K4 mono-methylation (H3K4me1), and the conversion to active enhancers involves acetylation of histone H3K27 (H3K27Ac). However, whether active enhancers are regulated remains unclear. Here we report a biochemical complex consisting of a potential chromatin reader (RACK7) and a histone demethylase (KDM5C) that occupies many active enhancers in a breast cancer cell line. Loss of RACK7 or KDM5C results in hyperactive enhancers marked by H3K4me3 and H3K27Ac, and characterized by an increased eRNA transcription and elevated expression of nearby genes. Loss of RACK7 or KDM5C also leads to increased cell invasion and migration, and enhanced tumor growth. We propose that RACK7/KDM5C functions as an enhancer âbrakeâ to ensure appropriate enhancer activities in the cell. Our findings provide important insight into histone H3K4 methylation dynamics at enhancers and reveal a molecular mechanism that controls the activities of active enhancers, which when compromised, can contribute to tumorigenesis. mRNA-seq of parental and RACK7-KO ZR-75-30 cells
2016-04-07 | E-GEOD-71325 | biostudies-arrayexpress
Project description:Primed enhancers are marked by histone H3K4 mono-methylation (H3K4me1), and the conversion to active enhancers involves acetylation of histone H3K27 (H3K27Ac). However, whether active enhancers are regulated remains unclear. Here we report a biochemical complex consisting of a potential chromatin reader (RACK7) and a histone demethylase (KDM5C) that occupies many active enhancers in a breast cancer cell line. Loss of RACK7 or KDM5C results in hyperactive enhancers marked by H3K4me3 and H3K27Ac, and characterized by an increased eRNA transcription and elevated expression of nearby genes. Loss of RACK7 or KDM5C also leads to increased cell invasion and migration, and enhanced tumor growth. We propose that RACK7/KDM5C functions as an enhancer âbrakeâ to ensure appropriate enhancer activities in the cell. Our findings provide important insight into histone H3K4 methylation dynamics at enhancers and reveal a molecular mechanism that controls the activities of active enhancers, which when compromised, can contribute to tumorigenesis. nascent RNA-seq of parental and RACK7-KO cells
2016-04-07 | E-GEOD-71326 | biostudies-arrayexpress
Project description:Primed enhancers are marked by histone H3K4 mono-methylation (H3K4me1), and the conversion to active enhancers involves acetylation of histone H3K27 (H3K27Ac). However, whether active enhancers are regulated remains unclear. Here we report a biochemical complex consisting of a potential chromatin reader (RACK7) and a histone demethylase (KDM5C) that occupies many active enhancers in a breast cancer cell line. Loss of RACK7 or KDM5C results in hyperactive enhancers marked by H3K4me3 and H3K27Ac, and characterized by an increased eRNA transcription and elevated expression of nearby genes. Loss of RACK7 or KDM5C also leads to increased cell invasion and migration, and enhanced tumor growth. We propose that RACK7/KDM5C functions as an enhancer âbrakeâ to ensure appropriate enhancer activities in the cell. Our findings provide important insight into histone H3K4 methylation dynamics at enhancers and reveal a molecular mechanism that controls the activities of active enhancers, which when compromised, can contribute to tumorigenesis. ChIP-seq data of RACK7, KDM5C and histone modifications in parental and RACK7-KO ZR-75-30 cells.
2016-04-07 | E-GEOD-71323 | biostudies-arrayexpress
Project description:Primed enhancers are marked by histone H3K4 mono-methylation (H3K4me1), and the conversion to active enhancers involves acetylation of histone H3K27 (H3K27Ac). However, whether active enhancers are regulated remains unclear. Here we report a biochemical complex consisting of a potential chromatin reader (RACK7) and a histone demethylase (KDM5C) that occupies many active enhancers in a breast cancer cell line. Loss of RACK7 or KDM5C results in hyperactive enhancers marked by H3K4me3 and H3K27Ac, and characterized by an increased eRNA transcription and elevated expression of nearby genes. Loss of RACK7 or KDM5C also leads to increased cell invasion and migration, and enhanced tumor growth. We propose that RACK7/KDM5C functions as an enhancer âbrakeâ to ensure appropriate enhancer activities in the cell. Our findings provide important insight into histone H3K4 methylation dynamics at enhancers and reveal a molecular mechanism that controls the activities of active enhancers, which when compromised, can contribute to tumorigenesis. ChIP-seq data of RACK7, KDM5C and histone modifications in parental and RACK7-KO ZR-75-30 cells.
2016-04-07 | E-GEOD-76637 | biostudies-arrayexpress
Project description:The Polycomb repressive complexes PRC1 and PRC2 play an essential role in cell fate decisions, embryonic development and gene regulation. While the functions of PRC2 in cancer are under intense study, the function of PRC1 in cancer remains largely unexplored. Here, we show that RNF2, the gene encoding RING1B, and canonical PRC1 (cPRC1) genes are amplified and overexpressed in breast cancer. Specifically, in estrogen receptor positive (ER+) breast cancer cells, cPRC1 is functionally associated with enhancers and genes regulated by ERa, while in triple negative breast cancer (TNBC) cells, a different cPRC1 variant is recruited to enhancers and promoters occupied by the bromodomain protein BRD4. Mechanistically, cPRC1 complexes are recruited to active enhancers independently of PRC2 and RING1B enzymatic activity. Moreover, RING1B has a dual role in regulating enhancer activity and gene transcription as it is recruited to enhancers to maintain and promote gene expression of breast cancer oncogenes. We also show that RING1B regulates chromatin accessibility of oncogenic transcription factors. Finally, we provide evidence that association of PRC1 to active enhancers is not restricted to breast cancer, demonstrating that RING1B recruitment to transcriptionally active sites occurs in multiple cancer types. Our work highlights a non-classical function of cPRC1 complexes in regulating specific oncogenic programs in cancer through its association with enhancer regions.
2018-08-30 | GSE107176 | GEO
Project description:Massively Parallel Genetic Disruption of Enhancers Active During Human Corticogenesis
| PRJNA577450 | ENA
Project description: Not available
| S-EPMC6284781 | biostudies-literature
Project description:The majority of all genes have so far been identified and annotated systematically through in silico gene finding. Here we report the finding of 3,217 strand-specific Transcriptionally Active Regions (TARs) in the genome of Bacillus subtilis by the use of tiling arrays. We have measured the genome-wide expression during mid-exponential growth on rich (LB) and minimal (M9) medium. The identified TARs account for 81.5% of the genes as they are currently annotated and additionally we find 44 novel protein-coding genes, 85 putative non-coding RNAs (ncRNAs) and 184 antisense transcripts. Hybridization of labeled genomic DNA (gDNA) has revealed a few thousand regions giving rise to very low signals. These are mostly caused by sequence errors, as is observed in the highly degenerate trp operon and the folding of stable structures such as the regions containing Rho-independent terminators. Through this work we have discovered a group of membrane-associated genes, among these having a long conserved 3â UnTranslated Region (UTR) predicted to fold into a large and highly stable structure. Among these are YwbN, a target of the twin-arginine translocase (Tat) protein translocation system. The transcriptionally active regions were determined at two different conditions, rich medium (Luria Broth) and minimal medium (M9). Cells were harvested at mid-exponential phase (OD600 = 0.5) and each condition were replicated three times. From each replicate RNA was extracted using FastRNA pro blue kit (Qbiogene) and labelled with Cy3 using a strand-specific protocol. The cDNA was hybridized to 385K NimbleGen tiling arrays 'BaSysBio Bsub T1' covering the entire genome with 45-65 nt isothermal probes, spaced by 22 nt on each strand. Additionally genomic DNA was extracted from 4 replicates at OD600 = 0.5, labelled and hybridized to the tiling arrays. These serve as a reference for the mRNA hybridizations. The normalized RNA hybridization signals were used to create segments using a structural change model (Huber et al, 2006) and transcriptionally active regions were identified by a segment joining-scheme.
2010-05-18 | E-GEOD-16086 | biostudies-arrayexpress