EurekaMag
+ Most Popular
Cunninghamia lanceolata plantations in China
Mammalian lairs in paleo ecological studies and palynology
Studies on technological possibilities in utilization of anhydrous milk fat for production of recombined butter-like products
Should right-sided fibroelastomas be operated upon?
Large esophageal lipoma
Apoptosis in the mammalian thymus during normal histogenesis and under various in vitro and in vivo experimental conditions
Poissons characoides nouveaux ou non signales de l'Ilha do Bananal, Bresil
Desensitizing efficacy of Colgate Sensitive Maximum Strength and Fresh Mint Sensodyne dentifrices
Administration of fluid by subcutaneous infusion: revival of a forgotten method
Tundra mosquito control - an impossible dream?
Schizophrenia for primary care providers: how to contribute to the care of a vulnerable patient population
Geochemical pattern analysis; method of describing the Southeastern limestone regional aquifer system
Incidence of low birth weights in a hospital of Mexico City
Tabanidae
Graded management intensity of grassland systems for enhancing floristic diversity
Microbiology and biochemistry of cheese and fermented milk
The ember tetra: a new pygmy characid tetra from the Rio das Mortes, Brazil, Hyphessobrycon amandae sp. n. (Pisces, Characoidei)
Risk factors of contrast-induced nephropathy in patients after coronary artery intervention
Renovation of onsite domestic wastewater in a poorly drained soil
Observations of the propagation velocity and formation mechanism of burst fractures caused by gunshot
Systolic blood pressure in a population of infants in the first year of life: the Brompton study
Haematological studies in rats fed with metanil yellow
Studies on pasteurellosis. I. A new species of Pasteurella encountered in chronic fowl cholera
Dormancy breaking and germination of Acacia salicina Lindl. seeds
therapy of lupus nephritis. a two-year prospective study

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


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



Genes and Development 26(22): 2499-2511



ISSN/ISBN: 0890-9369

PMID: 23105005

DOI: 10.1101/gad.200329.112

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.

Please choose payment method:






(PDF emailed within 0-6 h: $19.90)

Accession: 053339281

Download citation: RISBibTeXText

Related references

Characterization of combinatorial histone modifications on lineage-affiliated genes during hematopoietic stem cell myeloid commitment. Acta Biochimica et Biophysica Sinica 46(10): 894-901, 2014

Lineage commitment of hematopoietic stem cells and progenitors: insights from recent single cell and lineage tracing technologies. Experimental Hematology 88: 1-6, 2020

Expression and function of receptors for stem cell factor and erythropoietin during lineage commitment of human hematopoietic progenitor cells. Blood 88(5): 1594-1607, 1996

Myeloid lineage commitment from the hematopoietic stem cell. Arerugi 60(7): 817-822, 2011

Myeloid lineage commitment from the hematopoietic stem cell. Immunity 26(6): 726-740, 2007

SHIP1-expressing mesenchymal stem cells regulate hematopoietic stem cell homeostasis and lineage commitment during aging. Stem Cells and Development 24(9): 1073-1081, 2015

Hematopoietic stem/progenitor cell commitment to the megakaryocyte lineage. Blood 127(10): 1242-1248, 2016

Epigenetic Mechanisms: Role in Hematopoietic Stem Cell Lineage Commitment and Differentiation. Current Drug Targets 19(14): 1683-1695, 2018

The histone H2A deubiquitinase Usp16 regulates embryonic stem cell gene expression and lineage commitment. Nature Communications 5: 3818, 2014

Multifaceted Actions of GFI1 and GFI1B in Hematopoietic Stem Cell Self-Renewal and Lineage Commitment. Frontiers in Genetics 11: 591099, 2020

Distinct B-cell lineage commitment distinguishes adult bone marrow hematopoietic stem cells. Proceedings of the National Academy of Sciences of the United States of America 109(14): 5394-5398, 2012

Asymmetric division and lineage commitment at the level of hematopoietic stem cells: inference from differentiation in daughter cell and granddaughter cell pairs. Journal of Experimental Medicine 199(3): 295-302, 2004

RUNX1a enhances hematopoietic lineage commitment from human embryonic stem cells and inducible pluripotent stem cells. Blood 121(15): 2882-2890, 2013

Identification and expression analysis of novel transcriptional regulators of hematopoietic stem and progenitor cell development and lineage commitment. American Journal of Human Genetics 61(4 Suppl): A34, 1997

Snail1-dependent control of embryonic stem cell pluripotency and lineage commitment. Nature Communications 5: 3070, 2014