Molecular cloning and analysis of a group of genes differentially expressed in cells which overexpress the Hoxa-1 homeobox gene

Exp Cell Res. 2000 Aug 25;259(1):274-83. doi: 10.1006/excr.2000.4963.


The homeobox gene Hoxa-1 is transcriptionally regulated by retinoic acid (RA) and encodes a transcription factor which has been shown to play important roles in cell differentiation and embryogenesis. In order to clone and characterize target genes of Hoxa-1, we utilized differential hybridization screening and cDNA subtractive hybridization methods to identify genes which are differentially expressed in F9-10, a murine F9 teratocarcinoma stem cell line which expresses high levels of exogenous Hoxa-1, compared to F9 wild-type stem cells, which do not express endogenous Hoxa-1 mRNA in the absence of RA. Twenty-eight candidate genes were identified; these genes encode very diverse proteins, including signaling molecules such as BMP-4, the enzyme superoxide dismutase, the cell adhesion molecule cadherin-6, proteins involved in gene transcription such as HMG-1 and SAP18, homeodomain-containing proteins Gbx-2 and Evx-2, and cell cycle regulatory proteins such as the retinoblastoma binding protein-2. Clone 104 encodes a novel protein; the expression of the clone 104 mRNA is also regulated in a fashion very similar to that of the exogenous Hoxa-1 gene in another F9 cell line, called F9-tet-Hoxa1-8, in which the exogenous Hoxa-1 mRNA expression is tightly regulated by a Tet-off gene expression system. These data strongly suggest that clone 104 is a direct downstream target of the transcription factor Hoxa-1. The cDNA sequence of clone 104 is related to that of human ubiquitin carboxyl-terminal hydrolase T. Further characterization of these putative Hoxa-1 target genes will aid in delineating the functions of the Hoxa-1 protein in the differentiation processes which occur during embryogenesis.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Bone Morphogenetic Protein 4
  • Bone Morphogenetic Proteins / genetics
  • Cadherins / genetics
  • Carrier Proteins / genetics
  • Cell Differentiation / genetics
  • Cloning, Molecular / methods*
  • Co-Repressor Proteins
  • Gene Expression / physiology
  • Genetic Testing / methods
  • HMGB1 Protein
  • High Mobility Group Proteins / genetics
  • Histone Deacetylases
  • Homeodomain Proteins
  • Humans
  • Mice
  • Phosphoproteins / genetics
  • Proteins*
  • RNA, Messenger / analysis
  • RNA-Binding Proteins
  • Receptors, Retinoic Acid / genetics
  • Retinoblastoma-Like Protein p130
  • Stem Cells / cytology
  • Superoxide Dismutase / genetics
  • Teratocarcinoma
  • Trans-Activators / genetics*
  • Transcription Factors / genetics
  • Transcription, Genetic / physiology
  • Tumor Cells, Cultured
  • Ubiquitins / genetics


  • BMP4 protein, human
  • Bmp4 protein, mouse
  • Bone Morphogenetic Protein 4
  • Bone Morphogenetic Proteins
  • Cadherins
  • Carrier Proteins
  • Co-Repressor Proteins
  • HMGB1 Protein
  • High Mobility Group Proteins
  • Homeodomain Proteins
  • Phosphoproteins
  • Proteins
  • RBL2 protein, human
  • RNA, Messenger
  • RNA-Binding Proteins
  • Rbl2 protein, mouse
  • Receptors, Retinoic Acid
  • Retinoblastoma-Like Protein p130
  • SAP18 protein, human
  • Sap18 protein, mouse
  • Trans-Activators
  • Transcription Factors
  • Ubiquitins
  • HoxA protein
  • Superoxide Dismutase
  • Histone Deacetylases
  • K cadherin