Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

RNA LEVER mediates long-range regulation of ε-globin by keeping PRC2 in check

ABSTRACT: EZH2, a core component of polycomb repressive complex 2 (PRC2), is a histone H3 methyltransferase required for gene silencing during embryonic development. The regulatory function of promiscuous binding of RNA to EZH2 is not known, although evidences suggest that binding of RNA inactivates EZH2 in vitro. Here we present a seesaw mechanism for the regulation of ε-globin through inactivating EZH2 by an upstream RNA (LEVER) in K562 cells. We show that LEVER, identified by RNA immune precipitation sequencing (RIP-seq) and NANOPORE sequencing, binds EZH2 and thereby preventing the accumulation of H3K27 methylation along the axis where LEVER emerges. The opened chromatin within LEVER in turn competes for the DNA looping between the locus control region (LCR) and the promoter of ε-globin. Hence, LEVER downregulates ε-globin by inhibiting EZH2.

ORGANISM(S): Homo sapiens

PROVIDER: GSE141083 | GEO | 2022/02/15

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

RNA LEVER mediates long-range regulation of ε-globin by keeping PRC2 in check

Project description:RNA LEVER mediates long-range regulation of ε-globin by keeping PRC2 in check

| PRJNA591956 | ENA

Epigenetic modifications and chromosome conformations of the beta globin locus throughout development

Project description:Human embryonic stem cells provide an alternative to using human embryos for studying developmentally regulated gene expression. The co-expression of high levels of embryonic epsilon and fetal gamma globin by the hESC-derived erythroblasts allows the interrogation of epsilon globin regulation at the transcriptional and epigenetic level which could only be attained previously by studying cell lines or transgenic mice. In this study, we compared the histone modifications across the beta globin locus of the undifferentiated hESCs and hESC-, FL-, and mobilized PB CD34+ cells-derived erythroblasts, which have distinct globin expression patterns corresponding to their developmental stages. We demonstrated that the histone codes employed by the beta globin locus are conserved throughout development. Furthermore, in spite of the close proximity of the epsilon globin promoter, as compared to the gamma or beta globin promoter, with the LCR, a chromatin loop was also formed between the LCR and the active epsilon globin promoter, similar to the loop that forms between the gamma or beta globin promoters and the LCR, in contrary to the previously proposed tracking mechanism. Human embryonic stem cells, hESC-, FL-, and PB derived erythroblasts were studied. The enrichment of H3K4me3 and AcH3 acrossed the beta globin locus was studied using ChIP-seq.

2015-01-26 | E-GEOD-35375 | biostudies-arrayexpress

Epigenetic modifications and chromosome conformations of the beta globin locus throughout development

2015-01-26 | GSE35375 | GEO

Distinct Ldb1/NLI complexes orchestrate γ-globin repression and re-activation through ETO2 in human adult erythroid cells.

Project description:The Ldb1/GATA-1/TAL1/LMO2 complex mediates long range interaction between the β-globin locus control region (LCR) and gene in adult mouse erythroid cells but whether this complex mediates chromatin interactions at other developmental stages or in human cells is unknown. We investigated human NLI (Ldb1 homologue) complex occupancy and chromatin conformation of the β-globin locus in human erythroid cells. In addition to the LCR, we find robust NLI complex occupancy at a site downstream of the Aγ-globin gene, within sequences of BGL3, an intergenic RNA transcript. In cells primarily transcribing β-globin, BGL3 is not transcribed and BGL3 sequences are occupied by NLI core complex members together with co-repressor ETO2 and γ-globin repressor BCL11A. The LCR and β-globin gene establish proximity in these cells. In contrast, when γ-globin transcription is re-activated by cytokines in these cells, ETO2 participation in the NLI complex at BGL3 is diminished, as is BCL11A occupancy, and both BGL3 and γ-globin are transcribed. In these cells, proximity between the BGL3/γ-globin region and the LCR is established. Thus, alternative NLI complexes mediate γ-globin transcription or silencing through long range LCR interactions involving an intergenic site of non-coding RNA transcription and ETO2 is critical to this process. ChIP-chip of GATA-1, NLI, and pol II in cell lines Comparison of GATA-1, NLI, and pol II binding on chromatin. 2 replicates for each protein; ChIP and input DNA for each replicate

2012-01-05 | E-GEOD-30047 | biostudies-arrayexpress

Distinct Ldb1/NLI complexes orchestrate γ-globin repression and re-activation through ETO2 in human adult erythroid cells.

2012-01-05 | GSE30047 | GEO

Transcriptomic changes associated with DNA pol epsilon deficiency

Project description:What is the impact of DNA pol epsilon deficiency on gene expression as well as on the expression of ncRNA, gene silencing? To further investigate the effects of DPB2 over-expression, the transcriptome of DPB2OE lines 1 and 3 was compared to that of wild-type plants by RNA sequencing. Plantlets were grown in vitro on half strength MS for 9 days and used for total RNA extraction. mRNA seq on wild-type Col-0, two DPB2 overexpression lines and one abo4-1 mutant knock out.

2016-07-22 | E-GEOD-71002 | biostudies-arrayexpress

Editing the core region in HPFH deletions alters fetal and adult globin expression for treatment of β-hemoglobinopathies [4C]

Project description:We have identified putative repressor region (PRR) to exon-1 of β-globin (βE1) in the β-globin cluster as a core region in alll the HPFH deletions that activates fetal hemoglobin and silences adult hemoglobin. To test the impact of PRR-βE1 gene editing in β-globin cluster configuration, we employed Circular chromosome conformation capture (4C) analysis to assess the LCR interaction to the gamma-globin promoter. Using HBG2 promoter as viewpoint,4C analysis showed an increased interaction of HBG promoter to the hypersensitive (HS) sites of the LCR in HUDEP-2 clones harbouring PRR-βE1 biallelic deletions compared to control HUDEP-2 cells. Link for 4C output files Mendeley - Venkatesan, Vigneshwaran (2022), “4C data set ”, Mendeley Data, V1, doi: 10.17632/cz3thnr9kf.1

2022-04-26 | GSE201388 | GEO

Developmental stage specific chromosome architecture in human erythroid cells (Hi-C)

Project description:Chromatin structure is tightly intertwined with transcription regulation. Here we compared the chromosomal architectures of fetal and adult human erythroblasts and find that globally, chromatin structures and compartments A/B are highly similar at both developmental stages. At a finer scale, we detect distinct folding patterns at the developmentally controlled b-globin locus. Specifically, new fetal stage-specific contacts are uncovered between a region separating the fetal (g-) and adult (b-) globin genes (encompassing the HBBP1 and BGLT3 non-coding genes) and two distal chromosomal sites (HS5 and 3'HS1) that flank the locus. In contrast, in adult cells the HBBP1-BGLT3 region contacts the embryonic e-globin gene, physically separating the fetal globin genes from the enhancer (LCR). Removal of the HBBP1 gene strongly reactivates g-globin expression, accompanied by increased LCR-g-globin and decreased BGLT3-e-globin interactions, mimicking the effects of deleting the fetal globin repressor BCL11A. Our results uncover a new critical regulatory region as a potential target for therapeutic genome editing for hemoglobinopathies and highlight the power of chromosome conformation analysis in discovering new cis control elements.

2017-09-18 | GSE102197 | GEO

Developmental stage specific chromosome architecture in human erythroid cells (Capture-C)

2017-09-18 | GSE102186 | GEO

Developmental stage specific chromosome architecture in human erythroid cells (ChIP-seq)

2017-09-18 | GSE102184 | GEO