Impaired placental trophoblast lineage differentiation in Alkbh1(-/-) mice. Academic Article Article uri icon

Overview

MeSH

  • AlkB Homolog 1, Histone H2a Dioxygenase
  • Animals
  • Cluster Analysis
  • DNA-(Apurinic or Apyrimidinic Site) Lyase
  • Euchromatin
  • Fluorescent Antibody Technique
  • Gene Expression Profiling
  • HSP40 Heat-Shock Proteins
  • Immunoprecipitation
  • In Situ Hybridization
  • Mice
  • Mice, Knockout
  • Models, Genetic
  • Molecular Chaperones
  • Reverse Transcriptase Polymerase Chain Reaction
  • Two-Hybrid System Techniques

MeSH Major

  • Cell Differentiation
  • Dioxygenases
  • Gene Expression Regulation, Developmental
  • Phylogeny
  • Placenta
  • Transcription Factors
  • Trophoblasts

abstract

  • E. coli AlkB has been intensively studied since 1983, but the in vivo roles of its mammalian homologue Alkbh1 are unknown. We, therefore, created null mice for Alkbh1. Alkbh1 mRNA is expressed at highest levels in the trophoblast lineages of the developing placenta. Alkbh1(-/-) placentas have decreased expression of differentiated trophoblast markers including Tpbp, Gcm1, and Pl-1, and increased expression of the trophoblast stem cell marker Eomes. Alkbh1 localizes to nuclear euchromatin, and interacts strongly with Mrj, an essential placental gene that mediates gene repression by recruitment of class II histone deacetylases (HDACs). Competition experiments show Alkbh1 and HDAC4 binding to Mrj are mutually exclusive, which causes decreased HDAC activity and increased target gene expression. Our study demonstrates Alkbh1 performs important functions in placental trophoblast lineage differentiation and participates in mechanisms of transcriptional regulation.

publication date

  • February 2008

has subject area

  • AlkB Homolog 1, Histone H2a Dioxygenase
  • Animals
  • Cell Differentiation
  • Cluster Analysis
  • DNA-(Apurinic or Apyrimidinic Site) Lyase
  • Dioxygenases
  • Euchromatin
  • Fluorescent Antibody Technique
  • Gene Expression Profiling
  • Gene Expression Regulation, Developmental
  • HSP40 Heat-Shock Proteins
  • Immunoprecipitation
  • In Situ Hybridization
  • Mice
  • Mice, Knockout
  • Models, Genetic
  • Molecular Chaperones
  • Phylogeny
  • Placenta
  • Reverse Transcriptase Polymerase Chain Reaction
  • Transcription Factors
  • Trophoblasts
  • Two-Hybrid System Techniques

Research

keywords

  • Comparative Study
  • Journal Article

Identity

Language

  • eng

Digital Object Identifier (DOI)

  • 10.1002/dvdy.21418

PubMed ID

  • 18163532

Additional Document Info

start page

  • 316

end page

  • 327

volume

  • 237

number

  • 2