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NSD3-short is an adaptor protein that couples BRD4 to the CHD8 chromatin remodeler

ABSTRACT: This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

ORGANISM(S): Mus musculus

SUBMITTER: Christopher Vakoc

PROVIDER: E-GEOD-71186 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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NSD3-short is an adaptor protein that couples BRD4 to the CHD8 chromatin remodeler (ChIP-Seq)

Project description:The bromodomain and extraterminal (BET) protein BRD4 is a therapeutic target in acute myeloid leukemia (AML). Here, we demonstrate that the AML maintenance function of BRD4 requires its interaction with NSD3, which belongs to a subfamily of H3K36 methyltransferases. Unexpectedly, AML cells were found to only require a short isoform of NSD3 that lacks the methyltransferase domain. We show that NSD3-short is an adaptor protein that sustains leukemia by linking BRD4 to the CHD8 chromatin remodeler, by using a PWWP chromatin reader module, and by employing an acidic transactivation domain. Genetic targeting of NSD3 or CHD8 mimics the phenotypic and transcriptional effects of BRD4 inhibition. Furthermore, BRD4, NSD3, and CHD8 colocalize across the AML genome, and each is released from super-enhancer regions upon chemical inhibition of BET bromodomains. These findings suggest that BET inhibitors exert therapeutic effects in leukemia by evicting BRD4-NSD3-CHD8 complexes from chromatin to suppress transcription. ChIP-Seq for regulatory factors of BRD4, NSD3, CHD8 and histone modification H3K36me2 in MLL-AF9 transformed acute myeloid leukemia cells (RN2)

2015-12-17 | E-GEOD-71183 | biostudies-arrayexpress

NSD3-short is an adaptor protein that couples BRD4 to the CHD8 chromatin remodeler (RNA-Seq)

Project description:The bromodomain and extraterminal (BET) protein BRD4 is a therapeutic target in acute myeloid leukemia (AML). Here, we demonstrate that the AML maintenance function of BRD4 requires its interaction with NSD3, which belongs to a subfamily of H3K36 methyltransferases. Unexpectedly, AML cells were found to only require a short isoform of NSD3 that lacks the methyltransferase domain. We show that NSD3-short is an adaptor protein that sustains leukemia by linking BRD4 to the CHD8 chromatin remodeler, by using a PWWP chromatin reader module, and by employing an acidic transactivation domain. Genetic targeting of NSD3 or CHD8 mimics the phenotypic and transcriptional effects of BRD4 inhibition. Furthermore, BRD4, NSD3, and CHD8 colocalize across the AML genome, and each is released from super-enhancer regions upon chemical inhibition of BET bromodomains. These findings suggest that BET inhibitors exert therapeutic effects in leukemia by evicting BRD4-NSD3-CHD8 complexes from chromatin to suppress transcription. PolyA+ (illumine TruSeq)/not-so-random (NSR) primers selected RNA-Seq for shRNA/sgRNA-expressing MLL-AF9 transformed acute myeloid leukemia cells (RN2).

2015-12-17 | E-GEOD-71185 | biostudies-arrayexpress

BET inhibition releases the Mediator complex from specific cis elements in acute myeloid leukemia cells

Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

2016-03-01 | E-GEOD-74651 | biostudies-arrayexpress

Hematopoietic transcription factors and p300/CBP shape the effects of BET bromodomain inhibition in leukemia

Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

2015-05-01 | E-GEOD-66123 | biostudies-arrayexpress

NSD3-Short Is an Adaptor Protein that Couples BRD4 to the CHD8 Chromatin Remodeler.

| S-EPMC4688131 | biostudies-literature

NSD3-short is an adaptor protein that couples BRD4 to the CHD8 chromatin remodeler

Project description:This SuperSeries is composed of the SubSeries listed below.

2015-12-17 | GSE71186 | GEO

NSD3-short is an adaptor protein that couples BRD4 to the CHD8 chromatin remodeler (RNA-Seq)

2015-12-17 | GSE71185 | GEO

NSD3-short is an adaptor protein that couples BRD4 to the CHD8 chromatin remodeler (ChIP-Seq)

2015-12-17 | GSE71183 | GEO

BET inhibition releases the Mediator complex from specific cis elements in acute myeloid leukemia cells (ChIP-Seq I)

Project description:Genome occupancy profiling by high throughput sequencing ChIP-seq of Brd4 and Mediator with or without JQ1 treatment in MLL-AF9 transformed acute myeloid leukemia cells (RN2)

2016-03-01 | E-GEOD-74536 | biostudies-arrayexpress

BET inhibition releases the Mediator complex from specific cis elements in acute myeloid leukemia cells (ChIP-Seq II)

Project description:Genome occupancy profiling by high throughput sequencing ChIP-seq of Brd4 with or without Doxycycline treatment to induce Med12 or Med23 shRNAs in MLL-AF9 transformed acute myeloid leukemia cells (RN2)

2016-03-01 | E-GEOD-78221 | biostudies-arrayexpress

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