A short Gfi-1B isoform controls erythroid differentiation by recruiting the LSD1-CoREST complex through the dimethylation of its SNAG domain

J Cell Sci. 2012 Feb 15;125(Pt 4):993-1002. doi: 10.1242/jcs.095877. Epub 2012 Mar 7.


Gfi-1B is a transcriptional repressor essential for the regulation of erythropoiesis and megakaryopoiesis. Here we identify Gfi-1B p32, a Gfi-1B isoform, as essential for erythroid differentiation. Gfi-1B p32 is generated by alternative splicing and lacks the two first zinc finger domains of the protein. Selective knock down of Gfi-1B p32 compromises erythroid differentiation, whereas its ectopic expression induces erythropoiesis in the absence of erythropoietin. Gfi-1B p32 isoform binds to Gfi-1B target gene promoters and associates with the LSD1-CoREST repressor complex more efficiently than the major Gfi-1B p37 isoform. Furthermore, we show that Gfi-1B includes a KSKK motif in its SNAG domain, which recruits the repressor complex only when dimethylated on lysine 8. Mutation of lysine 8 prevents Gfi-1B p32-induced erythroid development. Our results thus highlight a key role for the alternatively spliced Gfi-1B p32 isoform in erythroid development.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alternative Splicing
  • Amino Acid Motifs
  • Cell Line
  • Co-Repressor Proteins
  • Erythropoiesis* / genetics
  • Erythropoietin
  • Gene Expression Regulation, Developmental
  • Histone Demethylases / metabolism*
  • Humans
  • Lysine / metabolism
  • Methylation
  • Molecular Weight
  • Nerve Tissue Proteins / metabolism*
  • Promoter Regions, Genetic / genetics
  • Protein Binding
  • Protein Isoforms / chemistry
  • Protein Isoforms / genetics
  • Protein Isoforms / metabolism
  • Protein Structure, Tertiary
  • Proto-Oncogene Proteins / chemistry*
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins / metabolism*
  • Repressor Proteins / chemistry*
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism*
  • Zinc Fingers


  • Co-Repressor Proteins
  • GFI1B protein, human
  • Nerve Tissue Proteins
  • Protein Isoforms
  • Proto-Oncogene Proteins
  • RCOR1 protein, human
  • Repressor Proteins
  • Erythropoietin
  • Histone Demethylases
  • KDM1A protein, human
  • Lysine