Transcriptomics

Dataset Information

63

Genome wide mapping of NR4A binding reveals cooperativity with ETS factors to promote epigenetic activation of distal enhancers in acute myeloid leukemia cells [array]


ABSTRACT: NR4As are critical tumor suppressors of acute myeloid leukemia (AML) whose expression is broadly silenced in leukemia initiating cell enriched populations from human patients relative to normal hematopoietic stem/progenitor cells. Rescued NR4A expression in human AML cells inhibits proliferation and reprograms AML gene signatures via transcriptional mechanisms that remain to be elucidated. By intersecting an acutely regulated, NR4A1 dependent transcriptional profile with genome wide NR4A binding distribution, we now identify an NR4A targetome of 685 genes that are directly regulated by NR4A1. We show that NR4As regulate gene transcription primarily through interaction with distal enhancers that are co-enriched for both NR4A1 and ETS transcription factor motifs. Using a subset of NR4A activated genes, we demonstrate that the ETS factors ERG and FLI-1 are required for activation of NR4A bound enhancers and NR4A target gene induction. NR4A1 dependent recruitment of ERG and FLI-1 promotes binding of p300 histone acetyl transferase to activate NR4A bound enhancers. These findings disclose novel epigenetic mechanisms by which NR4As and ETS factors cooperate to drive NR4A dependent gene transcription in human AML cells. Transcriptome analysis in triplicate 6hr after exogenous NR4A1 expression compared to GFP transfection control.

ORGANISM(S): Homo sapiens  

SUBMITTER: Seth P Boudreaux   Orla M Conneely  Orla Conneely  Ryan P Duren 

PROVIDER: E-GEOD-79490 | ArrayExpress | 2016-03-22

SECONDARY ACCESSION(S): GSE79490PRJNA315978

REPOSITORIES: GEO, ArrayExpress

altmetric image

Publications

Genome Wide Mapping of NR4A Binding Reveals Cooperativity with ETS Factors to Promote Epigenetic Activation of Distal Enhancers in Acute Myeloid Leukemia Cells.

Duren Ryan P RP   Boudreaux Seth P SP   Conneely Orla M OM  

PloS one 20160303 3


Members of the NR4A subfamily of orphan nuclear receptors regulate cell fate decisions via both genomic and non-genomic mechanisms in a cell and tissue selective manner. NR4As play a key role in maintenance of hematopoietic stem cell homeostasis and are critical tumor suppressors of acute myeloid leukemia (AML). Expression of NR4As is broadly silenced in leukemia initiating cell enriched populations from human patients relative to normal hematopoietic stem/progenitor cells. Rescue of NR4A expres  ...[more]

Similar Datasets

2016-03-22 | E-GEOD-79491 | ArrayExpress
2013-12-30 | E-GEOD-31042 | ArrayExpress
| GSE89970 | GEO
2015-06-30 | E-GEOD-70417 | ArrayExpress
2014-02-18 | E-GEOD-55078 | ArrayExpress
2014-10-27 | E-GEOD-31042 | ExpressionAtlas
| GSE73616 | GEO
| GSE23730 | GEO
2014-10-31 | E-GEOD-53665 | ArrayExpress
2012-09-18 | E-GEOD-23730 | ArrayExpress