Identification and characterization of FAM124B as a novel component of a CHD7 and CHD8 containing complex

PLoS One. 2012;7(12):e52640. doi: 10.1371/journal.pone.0052640. Epub 2012 Dec 21.


Background: Mutations in the chromodomain helicase DNA binding protein 7 gene (CHD7) lead to CHARGE syndrome, an autosomal dominant multiple malformation disorder. Proteins involved in chromatin remodeling typically act in multiprotein complexes. We previously demonstrated that a part of human CHD7 interacts with a part of human CHD8, another chromodomain helicase DNA binding protein presumably being involved in the pathogenesis of neurodevelopmental (NDD) and autism spectrum disorders (ASD). Because identification of novel CHD7 and CHD8 interacting partners will provide further insights into the pathogenesis of CHARGE syndrome and ASD/NDD, we searched for additional associated polypeptides using the method of stable isotope labeling by amino acids in cell culture (SILAC) in combination with mass spectrometry.

Principle findings: The hitherto uncharacterized FAM124B (Family with sequence similarity 124B) was identified as a potential interaction partner of both CHD7 and CHD8. We confirmed the result by co-immunoprecipitation studies and showed a direct binding to the CHD8 part by direct yeast two hybrid experiments. Furthermore, we characterized FAM124B as a mainly nuclear localized protein with a widespread expression in embryonic and adult mouse tissues.

Conclusion: Our results demonstrate that FAM124B is a potential interacting partner of a CHD7 and CHD8 containing complex. From the overlapping expression pattern between Chd7 and Fam124B at murine embryonic day E12.5 and the high expression of Fam124B in the developing mouse brain, we conclude that Fam124B is a novel protein possibly involved in the pathogenesis of CHARGE syndrome and neurodevelopmental disorders.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CHARGE Syndrome / genetics
  • CHARGE Syndrome / metabolism
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism*
  • Central Nervous System / metabolism
  • Cloning, Molecular
  • DNA Helicases / metabolism*
  • DNA-Binding Proteins / metabolism*
  • Gene Expression
  • Gene Expression Regulation, Developmental
  • HeLa Cells
  • Humans
  • Mice
  • Multiprotein Complexes / chemistry
  • Multiprotein Complexes / metabolism*
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism*
  • Organ Specificity / genetics
  • Protein Binding
  • Protein Transport
  • Transcription Factors / metabolism*
  • Transcription, Genetic


  • CHD8 protein, human
  • Carrier Proteins
  • DNA-Binding Proteins
  • FAM124B protein, human
  • FAM124B protein, mouse
  • Multiprotein Complexes
  • Nuclear Proteins
  • Transcription Factors
  • DNA Helicases
  • CHD7 protein, human

Grant support

This work was supported by the Deutsche Forschungsgemeinschaft (DFG) ( (PA 2030/1-1) to SP. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.