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Publication

Retinoid-Sensitive Epigenetic Regulation of the Hoxb Cluster Maintains Normal Hematopoiesis and Inhibits Leukemogenesis.

Cell stem cell | 2018

Hox genes modulate the properties of hematopoietic stem cells (HSCs) and reacquired Hox expression in progenitors contributes to leukemogenesis. Here, our transcriptome and DNA methylome analyses revealed that Hoxb cluster and retinoid signaling genes are predominantly enriched in LT-HSCs, and this coordinate regulation of Hoxb expression is mediated by a retinoid-dependent cis-regulatory element, distal element RARE (DERARE). Deletion of the DERARE reduced Hoxb expression, resulting in changes to many downstream signaling pathways (e.g., non-canonical Wnt signaling) and loss of HSC self-renewal and reconstitution capacity. DNA methyltransferases mediate DNA methylation on the DERARE, leading to reduced Hoxb cluster expression. Acute myeloid leukemia patients with DNMT3A mutations exhibit DERARE hypomethylation, elevated HOXB expression, and adverse outcomes. CRISPR-Cas9-mediated specific DNA methylation at DERARE attenuated HOXB expression and alleviated leukemogenesis. Collectively, these findings demonstrate pivotal roles for retinoid signaling and the DERARE in maintaining HSCs and preventing leukemogenesis by coordinate regulation of Hoxb genes.

Pubmed ID: 29727682 RIS Download

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Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.

This is a list of tools and resources that we have found mentioned in this publication.

CD3e Monoclonal Antibody (145-2C11), APC, eBioscience (antibody)

RRID:AB_469316

This monoclonal targets CD3e

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CD117 (c-Kit) Monoclonal Antibody (2B8), APC, eBioscience (antibody)

RRID:AB_469431

This monoclonal targets CD117 (c-Kit)

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CD135 (Flt3) Monoclonal Antibody (A2F10), Biotin, eBioscience (antibody)

RRID:AB_466600

This monoclonal targets CD135 (Flt3)

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Mouse Anti-CD34 Monoclonal Antibody, Allophycocyanin Conjugated, Clone 581 (antibody)

RRID:AB_398614

This monoclonal targets CD34

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Ly-6A/E (Sca-1) Monoclonal Antibody (D7), PE-Cyanine7, eBioscience (antibody)

RRID:AB_469669

This monoclonal targets Ly-6A/E (Sca-1)

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Ly-6G/Ly-6C Monoclonal Antibody (RB6-8C5), PE-Cyanine5, eBioscience (antibody)

RRID:AB_468813

This monoclonal targets Ly-6G/Ly-6C

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CD38 (antibody)

RRID:AB_1727473

This monoclonal targets CD38

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Rabbit IgG Isotype Control (antibody)

RRID:AB_2532938

This isotype control targets Not Applicable

View all literature mentions

FITC anti-human Lineage Cocktail (CD3/14/19/20/56) (antibody)

RRID:AB_10644012

This monoclonal targets FITC anti-human Lineage Cocktail (CD3/14/19/20/56)

View all literature mentions

Mouse Anti-CD14 Monoclonal Antibody, FITC Conjugated, Clone M5E2 (antibody)

RRID:AB_396589

This monoclonal targets CD14

View all literature mentions

IgM Monoclonal Antibody (II/41), PE-Cyanine5, eBioscience (antibody)

RRID:AB_494222

This monoclonal targets IgM

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CD45R (B220) Monoclonal Antibody (RA3-6B2), PE-Cyanine5, eBioscience (antibody)

RRID:AB_468756

This monoclonal targets CD45R (B220)

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PE anti-mouse CD49b (antibody)

RRID:AB_313029

This monoclonal targets CD49b

View all literature mentions

CD45.2 Monoclonal Antibody (104), FITC, eBioscience (antibody)

RRID:AB_465062

This monoclonal targets CD45.2

View all literature mentions

Ly-6G/Ly-6C Monoclonal Antibody (RB6-8C5), APC-eFluor™ 780, eBioscience (antibody)

RRID:AB_1518804

This monoclonal targets Ly-6G/Ly-6C

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CD11b Monoclonal Antibody (M1/70), PE-Cyanine5, eBioscience (antibody)

RRID:AB_468715

This monoclonal targets CD11b

View all literature mentions

CD11b Monoclonal Antibody (M1/70), PE-Cyanine7, eBioscience (antibody)

RRID:AB_469588

This monoclonal targets CD11b

View all literature mentions

CD11b/Mac-1 (antibody)

RRID:AB_396860

This monoclonal targets CD11b/Mac-1

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CD8a Monoclonal Antibody (53-6.7), PE-Cyanine5, eBioscience (antibody)

RRID:AB_468707

This monoclonal targets CD8a

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CD45R (B220) Monoclonal Antibody (RA3-6B2), PE, eBioscience (antibody)

RRID:AB_465672

This monoclonal targets CD45R (B220)

View all literature mentions

CD45.1 Monoclonal Antibody (A20), PE-Cyanine5, eBioscience (antibody)

RRID:AB_468759

This monoclonal targets CD45.1

View all literature mentions

CD3e Monoclonal Antibody (145-2C11), PE-Cyanine5, eBioscience (antibody)

RRID:AB_468691

This monoclonal targets CD3e

View all literature mentions

NOT AN ANTIBODY Streptavidin APC-eFluor 780 100 ug (antibody)

RRID:AB_10366688

This unknown targets Biotin

View all literature mentions

Mouse Anti-CD99 Monoclonal Antibody, Phycoerythrin Conjugated, Clone T??12 (antibody)

RRID:AB_396040

This monoclonal targets CD99

View all literature mentions

CD4 Monoclonal Antibody (RM4-5), PE-Cyanine5, eBioscience (antibody)

RRID:AB_468699

This monoclonal targets CD4

View all literature mentions

Mouse Anti-Ki-67 Set Monoclonal Antibody, FITC Conjugated, Clone B56 (antibody)

RRID:AB_396302

This monoclonal targets Ki-67

View all literature mentions

CD34 Monoclonal Antibody (RAM34), FITC, eBioscience (antibody)

RRID:AB_465022

This monoclonal targets CD34

View all literature mentions

CD45.2 (antibody)

RRID:AB_10897142

This monoclonal targets CD45.2

View all literature mentions

Rabbit IgG Isotype Control (antibody)

RRID:AB_2532938

This isotype control targets Not Applicable

View all literature mentions

Mouse Anti-Ki-67 Set Monoclonal Antibody, FITC Conjugated, Clone B56 (antibody)

RRID:AB_396302

This monoclonal targets Ki-67

View all literature mentions

CD11b/Mac-1 (antibody)

RRID:AB_396860

This monoclonal targets CD11b/Mac-1

View all literature mentions

Mouse Anti-CD14 Monoclonal Antibody, FITC Conjugated, Clone M5E2 (antibody)

RRID:AB_396589

This monoclonal targets CD14

View all literature mentions

Mouse Anti-CD99 Monoclonal Antibody, Phycoerythrin Conjugated, Clone T??12 (antibody)

RRID:AB_396040

This monoclonal targets CD99

View all literature mentions

CD38 (antibody)

RRID:AB_1727473

This monoclonal targets CD38

View all literature mentions

Mouse Anti-CD34 Monoclonal Antibody, Allophycocyanin Conjugated, Clone 581 (antibody)

RRID:AB_398614

This monoclonal targets CD34

View all literature mentions

FITC anti-human Lineage Cocktail (CD3/14/19/20/56) (antibody)

RRID:AB_10644012

This monoclonal targets FITC anti-human Lineage Cocktail (CD3/14/19/20/56)

View all literature mentions

CD3e Monoclonal Antibody (145-2C11), APC, eBioscience (antibody)

RRID:AB_469316

This monoclonal targets CD3e

View all literature mentions

Ly-6G/Ly-6C Monoclonal Antibody (RB6-8C5), APC-eFluor™ 780, eBioscience (antibody)

RRID:AB_1518804

This monoclonal targets Ly-6G/Ly-6C

View all literature mentions

CD11b Monoclonal Antibody (M1/70), PE-Cyanine7, eBioscience (antibody)

RRID:AB_469588

This monoclonal targets CD11b

View all literature mentions

CD45.2 (antibody)

RRID:AB_10897142

This monoclonal targets CD45.2

View all literature mentions

PE anti-mouse CD49b (antibody)

RRID:AB_313029

This monoclonal targets CD49b

View all literature mentions

CD135 (Flt3) Monoclonal Antibody (A2F10), Biotin, eBioscience (antibody)

RRID:AB_466600

This monoclonal targets CD135 (Flt3)

View all literature mentions

Ly-6A/E (Sca-1) Monoclonal Antibody (D7), PE-Cyanine7, eBioscience (antibody)

RRID:AB_469669

This monoclonal targets Ly-6A/E (Sca-1)

View all literature mentions

IgM Monoclonal Antibody (II/41), PE-Cyanine5, eBioscience (antibody)

RRID:AB_494222

This monoclonal targets IgM

View all literature mentions

CD3e Monoclonal Antibody (145-2C11), PE-Cyanine5, eBioscience (antibody)

RRID:AB_468691

This monoclonal targets CD3e

View all literature mentions

CD34 Monoclonal Antibody (RAM34), FITC, eBioscience (antibody)

RRID:AB_465022

This monoclonal targets CD34

View all literature mentions

CD117 (c-Kit) Monoclonal Antibody (2B8), APC, eBioscience (antibody)

RRID:AB_469431

This monoclonal targets CD117 (c-Kit)

View all literature mentions

NOT AN ANTIBODY Streptavidin APC-eFluor 780 100 ug (antibody)

RRID:AB_10366688

This unknown targets Biotin

View all literature mentions

CD45R (B220) Monoclonal Antibody (RA3-6B2), PE, eBioscience (antibody)

RRID:AB_465672

This monoclonal targets CD45R (B220)

View all literature mentions

CD45.1 Monoclonal Antibody (A20), PE-Cyanine5, eBioscience (antibody)

RRID:AB_468759

This monoclonal targets CD45.1

View all literature mentions

CD45R (B220) Monoclonal Antibody (RA3-6B2), PE-Cyanine5, eBioscience (antibody)

RRID:AB_468756

This monoclonal targets CD45R (B220)

View all literature mentions

CD45.2 Monoclonal Antibody (104), FITC, eBioscience (antibody)

RRID:AB_465062

This monoclonal targets CD45.2

View all literature mentions

Ly-6G/Ly-6C Monoclonal Antibody (RB6-8C5), PE-Cyanine5, eBioscience (antibody)

RRID:AB_468813

This monoclonal targets Ly-6G/Ly-6C

View all literature mentions

CD11b Monoclonal Antibody (M1/70), PE-Cyanine5, eBioscience (antibody)

RRID:AB_468715

This monoclonal targets CD11b

View all literature mentions

CD8a Monoclonal Antibody (53-6.7), PE-Cyanine5, eBioscience (antibody)

RRID:AB_468707

This monoclonal targets CD8a

View all literature mentions

CD4 Monoclonal Antibody (RM4-5), PE-Cyanine5, eBioscience (antibody)

RRID:AB_468699

This monoclonal targets CD4

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