Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Bidirectional enhancer RNAs regulate different MYB promoters

ABSTRACT: MYB is a pivotal oncogenic driver in leukemia and is overexpressed through various mechanisms. Transcriptional regulation of MYB is complex with an alternative MYB promoter (TSS2) located in intron 1. Here, we identified two bidirectional enhancer RNAs transcribed from the -34 kb enhancer of MYB. These two eRNAs both upregulate MYB transcription, and promote proliferation and migration in leukemia cells. To further elucidate how eRNAs regulate MYB expression, we analyzed MYB differential exon usage in RNASeq data with the DEXSeq package after overexpression of eRNAs in K562 cells. We found that bidirectional enhancer RNAs regulate different MYB promoters. Transcription initiating from TSS2 produces N-terminally truncated MYB protein lacking the first 20 amino acids. To analyze the genes and pathways affected by both MYB isoforms, RNA-seq was performed after MYB or N-terminally truncated MYB was overexpressed in K562 cells. We found that N-terminally truncated MYB exhibits different activity in K562 cells, where it not only activates different primary targets, but also different downstream pathways altogether.

ORGANISM(S): Homo sapiens

PROVIDER: GSE263511 | GEO | 2024/08/01

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Functional Importance of eRNAs for Estrogen-dependent Gene Transcriptional Activation

Project description:The functional importance of gene enhancers in regulated gene expression is well established. In addition to widespread transcription of long non-coding RNA (ncRNA) transcripts in mammalian cells, bidirectional ncRNAs referred to as eRNAs are present on enhancers. However, it has remained unclear whether these eRNAs are functional, or merely a reflection of enhancer activation. Here, we report that 17 ?-estradiol (E2)-bound estrogen receptor alpha (ER?) on enhancers causes a global increase in eRNA transcription on enhancers adjacent to E2 upregulated coding genes. These induced eRNAs, as functional transcripts, appear to exert important roles for the observed ligand-dependent induction of target coding genes, causing an increased strength of specific enhancer:promoter looping initiated by ER? binding. Cohesin, present on many ER?-regulated enhancers even prior to ligand treatment, apparently contributes to E2-dependent gene activation by stabilizing E2/ER?/eRNA-induced enhancer:promoter looping. Our data indicate that eRNAs are likely to exert important functions in many regulated programs of gene transcription. The ChIP-seqs in this study measure the binding landscape of master transcription regulator of estrogen signaling - ER?, together with common histone marks including H3K27ac and H3K4me1 in MCF7 cells. These data serve as the basis to understand the enhancer map and subsequent analysis of eRNA expression using GRO-seq. The GRO-seq measures the trancription of nascent RNAs in the genome. From MCF7 cells treated with veichle or estrodial, we could identify estrogen-regulated eRNAs and subsequently could study their functions.

2013-06-04 | E-GEOD-45822 | biostudies-arrayexpress

Functional Importance of eRNAs for Estrogen-dependent Gene Transcriptional Activation

2013-06-04 | GSE45822 | GEO

Amplicon-seq of an enhancer region targeted by CRISPR to assess the mutations introduced by different sgRNA guides

Project description:Following a CRISPR enhancer scan covering the GATA2 super-enhancer region, the top sgRNAs were selected for further inspection. MUTZ3 cells were thus treated with the selected sgRNAs and the region of interested was subjected to amplicons sequencing (amplicon-seq). To that end, we used the Illumina PCR-based custom amplicon sequencing method using the TruSeq Custom Amplicon index kit (Illumina). The same experiment was conducted in K562 cells, which do not harbor an inv(3)/t(3;3), to investigate the role of MYB in this enhancer in other leukemia settings

2021-07-26 | E-MTAB-9945 | biostudies-arrayexpress

Enhancer RNAs stimulate Pol II pause release by harnessing multivalent interactions to NELF

Project description:UV-light-induced protein-RNA cross-linking followed by MS analysis was used to identify RNA-binding regions of enhancer RNAs (eRNAs) to the negative elongation factor (NELF) complex, and NELF as part of the paused elongation complex (PEC) of human RNA polymerase II.

2022-03-08 | PXD030569 | Pride

The histone variant H2A.Z is an important regulator of enhancer activity.

Project description:Gene regulatory programs in different cell types are largely defined through cell-specific enhancers activity. The histone variant H2A.Z has been shown to play important roles in transcription mainly by controlling proximal promoters, but its effect on enhancer functions remains unclear. Here, we demonstrate by genome-wide approaches that H2A.Z is present at a subset of active enhancers bound by the estrogen receptor alpha (ERα). We also determine that H2A.Z does not influence the local nucleosome positioning around ERα-enhancers using ChIP-sequencing at nucleosomal resolution and unsupervised pattern discovery. We further highlight that H2A.Z-enriched enhancers are associated with chromatin accessibility, H3K122ac enrichment and hypomethylated DNA. Moreover, upon estrogen stimulation, the enhancers occupied by H2A.Z produce enhancer RNAs (eRNAs), and recruit RNA polymerase II as well as RAD21, a member of the cohesin complex involved in chromatin interactions between enhancers and promoters. Importantly, their recruitment and eRNAs production are abolished by H2A.Z depletion, thereby revealing a novel functional link between H2A.Z occupancy and enhancer activity. Taken together, our findings suggest that H2A.Z acts as an important player for enhancer functions by establishing and maintaining a chromatin environment required for RNA polymerase II recruitment, eRNAs transcription and enhancer-promoters interactions, all essential attributes of enhancer activity. The MNase ChIP-seqs in this study measure the genome-wide binding landscape of H2A.Z, H3K4me1, H3K27ac and H3K4me3 in MCF-7 cells in the absence or presence of E2. Two biological replicates were done for each ChIP-seq experiment and for each condition, as well as, control input.

2015-08-31 | E-GEOD-57436 | biostudies-arrayexpress

LncRNA-dependent mechanisms of androgen receptor-regulated gene activation programs [GRO-seq II]

Project description:While thousands of long non-coding RNAs (lncRNAs) are expressed in higher eukaryotes, the potential regulatory roles of lncRNAs in regulated gene transcription programs remain rather poorly understood. Here, we report that two lncRNAs highly overexpressed in aggressive prostate cancer, PRNCR1 and PCGEM1, bind successively to the androgen receptor (AR) and strongly enhance both ligand-dependent and ligand-independent AR-mediated gene activation programs and proliferation in prostate cancer cells. Binding of PRNCR1 to the C-terminally acetylated AR on enhancers and its association with DOT1L appear to be required for recruitment of the second lncRNA, PCGEM, to the N-terminally methylated AR. Unexpectedly, recognition of the H3K4me3 promoter mark by the PHD finger-domain of Pygopus2, recruited by PCGEM1, proves to enhance selective looping of AR-bound enhancers to target gene promoters in these cells, revealing a novel aspect of ligand-induced enhancer-promoter interactions. In “resistant” prostate cancer cells, these overexpressed lncRNAs can interact with, and are required for the robust activation of both truncated and full length AR, causing DHT-independent activation of the AR transcriptional program and cell proliferation. Conditionally-expressed short hairpin RNA (shRNA)-mediated targeting of these lncRNAs in these resistant cancer cell lines strongly suppressed xenograft growth in vivo. Together, these results suggest that these overexpressed lncRNAs can potentially serve as a required component of castration-resistance in prostatic tumors.

2013-08-15 | GSE47806 | GEO

LncRNA-dependent mechanisms of androgen receptor-regulated gene activation programs [GRO-seq I]

2013-08-15 | GSE47805 | GEO

LncRNA-dependent mechanisms of androgen receptor-regulated gene activation programs [ChIRP-seq]

2013-08-15 | GSE47804 | GEO

Truncated protein isoforms generate diversity of protein localization and function in yeast

Project description:Genome-wide measurements of ribosome occupancy on mRNA transcripts have enabled global empirical identification of translated regions. These approaches have revealed an unexpected diversity of protein products, but high-confidence identification of new coding regions that entirely overlap annotated coding regions – including those that encode truncated protein isoforms – has remained challenging. Here, we develop a sensitive and robust algorithm focused on identifying N-terminally truncated proteins genome-wide, identifying 388 truncated protein isoforms, a more than 30-fold increase in the number known in budding yeast. We perform extensive experimental validation of these truncated proteins and define two general classes. The first set lack large portions of the annotated protein sequence and tend to be produced from a truncated transcript. We show two such cases, Yap5truncation and Pus1truncation, to have condition-specific regulation and functions that appear distinct from their respective annotated isoforms. The second set of N-terminally truncated proteins lack only a small region of the annotated protein and are less likely to be regulated by an alternative transcript isoform. Many localize to different subcellular compartments than their annotated counterpart, representing a common strategy for achieving dual localization of otherwise functionally identical proteins.

2024-04-16 | GSE235852 | GEO

Rev-Erbs repress macrophage gene expression by inhibiting enhancer-directed transcription

Project description:Rev-Erba and Rev-Erbb are nuclear receptors that regulate the expression of genes involved in the control of circadian rhythm, metabolism, and inflammatory responses. Rev-Erbs function as transcriptional repressors by recruiting NCoR/HDAC3 co-repressor complexes to Rev-Erb response elements in enhancers and promoters of target genes, but the molecular basis for cell-specific programs of repression is not known. Here, we present evidence that in macrophages, Rev-Erbs regulate target gene expression by inhibiting the functions of distal enhancers that are selected by macrophage lineage-determining factors, thereby establishing a macrophage-specific program of repression. Remarkably, the repressive functions of Rev-Erbs are associated with their ability to inhibit the transcription of enhancer-derived RNAs (eRNAs). Furthermore, targeted degradation of eRNAs at two enhancers subject to negative regulation by Rev-Erbs resulted in reduced expression of nearby mRNAs, implying a direct role of these eRNAs in enhancer function. By precisely defining eRNA start sites using a method that quantifies nascent 5' ends (5'-GRO-Seq), we show that transfer of full enhancer activity to a target promoter requires both the sequences mediating transcription factor binding and the specific sequences encoding the eRNA transcript. These studies provide evidence for direct roles of eRNAs in contributing to enhancer functions and suggest that Rev-Erbs act to suppress gene expression at a distance by repressing eRNA transcription. Using ChIPseq, GRO-seq, and 5'GRO-seq to determine mechanism of RevErb in transcriptional regulation in macrophages

2013-06-05 | E-GEOD-45914 | biostudies-arrayexpress

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data