ALKBH1 Is a Histone H2A Dioxygenase Involved in Neural Differentiation
2012
AlkBhomolog 1 (ALKBH1) is one of nine members of the family of mammalian
AlkBhomologs. Most Alkbh1−/− mice die during embryonic development, and survivors are characterized by defects in tissues originating from the
ectodermallineage. 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 immunoprecipitationrevealed 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
dioxygenasethat acts specifically on
histone H2A. Mass spectrometric analysis demonstrated that
histone H2Afrom Alkbh1−/− mice are improperly methylated. Our results suggest that ALKBH1 is involved in
neural developmentby modifying the methylation status of
histone H2A. Stem Cells 2012;30:2672–2682
Keywords:
-
Correction
-
Source
-
Cite
-
Save
54
References
74
Citations
NaN
KQI