Evidence map›Paper›PMID 24813891›Full record

ArticleCell reports2014

The histone methyltransferase activity of MLL1 is dispensable for hematopoiesis and leukemogenesis.

Bibhu P Mishra, Kristin M Zaffuto, Erika L Artinger, Tonis Org, Hanna K A Mikkola, Chao Cheng, Malek Djabali, Patricia Ernst

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell reports, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 99 papers.

0numbers the graph read from it
0cells of the map it votes in
99citing papers in PubMed
7.0field-weighted citation impact, top 2% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

99 citing papers in PubMed, 131 citations in OpenAlex.

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39 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors at 4 institutions in 2 countries.

Bibhu P MishraDepartment of Genetics, Geisel School of Medicine at Dartmouth, Hanover, NH 03755, USA.
Kristin M ZaffutoDepartment of Genetics, Geisel School of Medicine at Dartmouth, Hanover, NH 03755, USA.
Erika L ArtingerDepartment of Genetics, Geisel School of Medicine at Dartmouth, Hanover, NH 03755, USA.
Tonis OrgEli and Edythe Broad Center for Stem Cell Research and Regenerative Medicine, Department of Molecular, Cell and Developmental Biology, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Hanna K A MikkolaEli and Edythe Broad Center for Stem Cell Research and Regenerative Medicine, Department of Molecular, Cell and Developmental Biology, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Chao ChengDepartment of Genetics, Geisel School of Medicine at Dartmouth, Hanover, NH 03755, USA; Institute for Quantitative Biomedical Sciences, Geisel School of Medicine at Dartmouth, Hanover, NH 03755, USA; Norris Cotton Cancer Center, Geisel School of Medicine at Dartmouth, Hanover, NH 03755, USA.
Malek DjabaliLaboratoire de Biologie Cellulaire et Moléculaire du Contrôle de la Proliferation, Université Paul Sabatier-Toulouse III, Bât4R3-B1118 Route de Narbonne, 31062 Toulouse, France.
Patricia ErnstDepartment of Genetics, Geisel School of Medicine at Dartmouth, Hanover, NH 03755, USA; Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth, Hanover, NH 03755, USA; Norris Cotton Cancer Center, Geisel School of Medicine at Dartmouth, Hanover, NH 03755, USA. Electronic address: patricia.ernst@dartmouth.edu.
Dartmouth College · USBroad Center · USLaboratoire de Biologie Cellulaire et Moléculaire du Contrôle de la Prolifération · FRUniversity of California, Los Angeles · US

Funding

MLL Function in the Maintenance of the Blood Forming SystemR01HL090036 · NHLBI · UNIVERSITY OF COLORADO DENVER · PI ERNST, PATRICIA · 2007 to 2015
$3.8M
NHLBI NIH HHS HL090036NHLBI NIH HHS HL090036-S1NHLBI NIH HHS R01 HL090036
6 · The paper itself

Abstract

Despite correlations between histone methyltransferase (HMT) activity and gene regulation, direct evidence that HMT activity is responsible for gene activation is sparse. We address the role of the HMT activity for MLL1, a histone H3 lysine 4 (H3K4) methyltransferase critical for maintaining hematopoietic stem cells (HSCs). Here, we show that the SET domain, and thus HMT activity of MLL1, is dispensable for maintaining HSCs and supporting leukemogenesis driven by the MLL-AF9 fusion oncoprotein. Upon Mll1 deletion, histone H4 lysine 16 (H4K16) acetylation is selectively depleted at MLL1 target genes in conjunction with reduced transcription. Surprisingly, inhibition of SIRT1 is sufficient to prevent the loss of H4K16 acetylation and the reduction in MLL1 target gene expression. Thus, recruited MOF activity, and not the intrinsic HMT activity of MLL1, is central for the maintenance of HSC target genes. In addition, this work reveals a role for SIRT1 in opposing MLL1 function.

Indexed as

AnimalsGene Expression RegulationHematopoiesisHematopoietic Stem CellsHistone AcetyltransferasesHistone-Lysine N-MethyltransferaseMiceMyeloid-Lymphoid Leukemia ProteinSirtuin 1Transcription FactorsHistone AcetyltransferasesHistone-Lysine N-MethyltransferaseKat8 protein, mouseKmt2a protein, mouseMyeloid-Lymphoid Leukemia ProteinSirt1 protein, mouseSirtuin 1Transcription Factors

Identifiers

PMID24813891
PMCPMC4120120
OpenAlexW2108453860

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.