Evidence map›Paper›PMID 23105005›Full record

ArticleGenes & development2012

G9a/GLP-dependent histone H3K9me2 patterning during human hematopoietic stem cell lineage commitment.

Xiaoji Chen, Kyobi Skutt-Kakaria, Jerry Davison, Yang-Li Ou, Edward Choi, Punam Malik, Keith Loeb, Brent Wood, George Georges, Beverly Torok-Storb and 1 more

Open access · diamondAbstract read
In one paragraph

Article in Genes & development, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 90 papers.

0numbers the graph read from it
0cells of the map it votes in
90citing papers in PubMed
–field-weighted citation impact
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

90 citing papers in PubMed, 138 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. Review
  5. Article
  6. Article
  7. Article
  8. The G9a histone methyltransferase represses osteoclastogenesis and bone resorption by regulating NFATc1 function.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2024
    Article
  9. Review
  10. Article
  11. Review
  12. Exploring the Interplay between Bone Marrow Stem Cells and Obesity.International journal of molecular sciences · 2024
    Review
  13. Article
  14. Histone Methyltransferases G9a/International journal of molecular sciences · 2023
    Article
  15. Article
  16. Article
  17. Article
  18. Review
  19. Article
  20. Review

30 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

11 authors at 5 institutions in 2 countries.

Xiaoji ChenMolecular and Cell Biology (MCB) Program, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA.
Kyobi Skutt-Kakaria
Jerry Davison
Yang-Li Ou
Edward Choi
Punam Malik
Keith Loeb
Brent Wood
George Georges
Beverly Torok-Storb
Patrick J Paddison
Fred Hutch Cancer Center · USCape Town HVTN Immunology Laboratory / Hutchinson Centre Research Institute of South Africa · ZACincinnati Children's Hospital Medical Center · USSeattle Cancer Care Alliance · USThe Evergreen State College · US

Funding

Translational Bioimaging Core Shared ResourceP30CA015704 · NCI · FRED HUTCHINSON CANCER RESEARCH CENTER · PI Marian Esvelt · 1985 to 2026
$296.4M
Progenitor Cell Biology Consortium Administrative Coordinating CenterU01HL099997 · NHLBI · UNIVERSITY OF MARYLAND BALTIMORE · PI TERRIN, MICHAEL L · 2009 to 2015
$29.9M
CORE--VECTOR PRODUCTIONP30DK056465 · NIDDK · FRED HUTCHINSON CANCER RESEARCH CENTER · PI HEIMFELD, SHELLY · 1999 to 2014
$14.9M
Cincinnati Center for Clinical and Translational Sciences and TrainingUL1TR000077 · NCATS · UNIVERSITY OF CINCINNATI · PI HEUBI, JAMES E. · 2012 to 2014
$9.9M
Controlling Hematopoietic Lineage Commitment from ESC to PlateletsU01HL099993 · NHLBI · FRED HUTCHINSON CANCER RESEARCH CENTER · PI TOROK-STORB, BEVERLY J. · 2009 to 2015
$8.3M
NCATS NIH HHS UL1 TR000077NCI NIH HHS P30 CA015704NHLBI NIH HHS U01 HL099993NHLBI NIH HHS U01 HL099997NHLBI NIH HHS U01-HL099997NIDDK NIH HHS P30 DK056465NIDDK NIH HHS P30DK056465NIDDK NIH HHS P30 DK56465
6 · The paper itself

Abstract

G9a and GLP are conserved protein methyltransferases that play key roles during mammalian development through mono- and dimethylation of histone H3 Lys 9 (H3K9me1/2), modifications associated with transcriptional repression. During embryogenesis, large H3K9me2 chromatin territories arise that have been proposed to reinforce lineage choice by affecting high-order chromatin structure. Here we report that in adult human hematopoietic stem and progenitor cells (HSPCs), H3K9me2 chromatin territories are absent in primitive cells and are formed de novo during lineage commitment. In committed HSPCs, G9a/GLP activity nucleates H3K9me2 marks at CpG islands and other genomic sites within genic regions, which then spread across most genic regions during differentiation. Immunofluorescence assays revealed the emergence of H3K9me2 nuclear speckles in committed HSPCs, consistent with progressive marking. Moreover, gene expression analysis indicated that G9a/GLP activity suppresses promiscuous transcription of lineage-affiliated genes and certain gene clusters, suggestive of regulation of HSPC chromatin structure. Remarkably, HSPCs continuously treated with UNC0638, a G9a/GLP small molecular inhibitor, better retain stem cell-like phenotypes and function during in vitro expansion. These results suggest that G9a/GLP activity promotes progressive H3K9me2 patterning during HSPC lineage specification and that its inhibition delays HSPC lineage commitment. They also inform clinical manipulation of donor-derived HSPCs.

Indexed as

Cell DifferentiationAdultAnimalsCell LineageCells, CulturedChromatinCpG IslandsDNA MethylationDogsEnzyme InhibitorsGene Expression ProfilingGene Expression Regulation, DevelopmentalHematopoietic Stem CellsHistocompatibility AntigensHistone-Lysine N-MethyltransferaseHistonesChromatinEHMT1 protein, humanEHMT2 protein, humanEnzyme InhibitorsHistocompatibility AntigensHistone-Lysine N-MethyltransferaseHistonesQuinazolinesUNC 0638

Identifiers

PMID23105005
PMCPMC3505820
OpenAlexW2145992200

What OpenQuestion holds

Textmetadata
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.