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PMID: 22961808 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

ALKBH1 is a histone H2A dioxygenase involved in neural differentiation.

Stem cells (Dayton, Ohio) ·Vol. 30 ·No. 12 ·2012-12-00 ·Pages 2672-82

Ougland R, Lando D, Jonson I, Dahl JA, Moen MN, Nordstrand LM, Rognes T, Lee JT, Klungland A, Kouzarides T, Larsen E

Abstract

AlkB homolog 1 (ALKBH1) is one of nine members of the family of mammalian AlkB homologs. Most Alkbh1(-/-) mice die during embryonic development, and survivors are characterized by defects in tissues originating from the ectodermal lineage. In this study, we show that deletion of Alkbh1 prolonged the expression of pluripotency markers in embryonic stem cells and delayed the induction of genes involved in early differentiation. In vitro differentiation to neural progenitor cells (NPCs) displayed an increased rate of apoptosis in the Alkbh1(-/-) NPCs when compared with wild-type cells. Whole-genome expression analysis and chromatin immunoprecipitation revealed that ALKBH1 regulates both directly and indirectly, a subset of genes required for neural development. Furthermore, our in vitro enzyme activity assays demonstrate that ALKBH1 is a histone dioxygenase that acts specifically on histone H2A. Mass spectrometric analysis demonstrated that histone H2A from Alkbh1(-/-) mice are improperly methylated. Our results suggest that ALKBH1 is involved in neural development by modifying the methylation status of histone H2A.

MeSH Terms
AlkB Homolog 1, Histone H2a Dioxygenase Animals Apoptosis/genetics,physiology Cell Differentiation/genetics,physiology Cell Nucleus/enzymology DNA Methylation DNA-(Apurinic or Apyrimidinic Site) Lyase/deficiency,genetics,metabolism Embryonic Stem Cells/cytology,enzymology Epigenomics Histones/genetics,metabolism Mice Microarray Analysis Neural Stem Cells/cytology,enzymology Pluripotent Stem Cells/cytology,enzymology Transfection
Chemicals
Histones AlkB Homolog 1, Histone H2a Dioxygenase Alkbh1 protein, mouse DNA-(Apurinic or Apyrimidinic Site) Lyase
Authors & Affiliations
11 authors, click to expand affiliations / ORCID
Ougland Rune
Centre for Molecular Biology and Neuroscience, Institute of Medical Microbiology, Oslo University Hospital, Rikshospitalet and University of Oslo, Oslo, Norway.
Lando David
Jonson Ida
Dahl John A
Moen Marivi Nabong
Nordstrand Line M
Rognes Torbjørn
Lee Jeannie T
Klungland Arne
Kouzarides Tony
Larsen Elisabeth
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Article Info
Journal
Stem cells (Dayton, Ohio)
Abbr.
Stem Cells
ISSN
1549-4918
DOI
10.1002/stem.1228
Published
2012-12-00
Pages
2672-82
Language
English
Region
United States
NLM ID
9304532
PMCID
PMC3546389
Subset
IM
Grants
Wellcome Trust · 092096 · United Kingdom
External Links
PubMed source DOI: 10.1002/stem.1228 PMC Full Text View journal details
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