Tet1 is required for Rb phosphorylation during G1/S phase transition

Biochem Biophys Res Commun. 2013 May 3;434(2):241-4. doi: 10.1016/j.bbrc.2013.02.110. Epub 2013 Mar 28.

Abstract

DNA methylation plays an important role in many biological processes, including regulation of gene expression, maintenance of chromatin conformation and genomic stability. TET-family proteins convert 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC), which indicates that these enzymes may participate in DNA demethylation. The function of TET1 has not yet been well characterized in somatic cells. Here, we show that depletion of Tet1 in NIH3T3 cells inhibits cell growth. Furthermore, Tet1 knockdown blocks cyclin D1 accumulation in G1 phase, inhibits Rb phosphorylation and consequently delays entrance to G1/S phase. Taken together, this study demonstrates that Tet1 is required for cell proliferation and that this process is mediated through the Rb pathway.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blotting, Western
  • Cell Proliferation
  • Cyclin D1 / genetics
  • Cyclin D1 / metabolism
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • G1 Phase*
  • Gene Expression Regulation
  • Gene Knockdown Techniques
  • HEK293 Cells
  • Humans
  • Lentivirus / genetics
  • Lentivirus / metabolism
  • Mice
  • NIH 3T3 Cells
  • Phosphorylation
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins / metabolism*
  • RNA, Small Interfering / genetics
  • RNA, Small Interfering / metabolism
  • Retinoblastoma Protein / genetics
  • Retinoblastoma Protein / metabolism*
  • S Phase*
  • Transcription, Genetic
  • Transfection

Substances

  • CCND1 protein, human
  • DNA-Binding Proteins
  • Proto-Oncogene Proteins
  • RNA, Small Interfering
  • Retinoblastoma Protein
  • TET1 protein, mouse
  • Cyclin D1