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BP1, a homeodomain-containing isoform of DLX4, represses the beta-globin gene.

Publication ,  Journal Article
Chase, MB; Fu, S; Haga, SB; Davenport, G; Stevenson, H; Do, K; Morgan, D; Mah, AL; Berg, PE
Published in: Mol Cell Biol
April 2002

In earlier studies we identified a putative repressor of the human beta-globin gene, termed beta protein 1 (BP1), which binds to two silencer DNA sequences upstream of the adult human beta-globin gene and to a negative control region upstream of the adult delta-globin gene. Further studies demonstrated an inverse correlation between the binding affinity of the BP1 protein for the distal beta-globin silencer sequence and the severity of sickle cell anemia, suggesting a possible role for BP1 in determining the production of hemoglobin S. We have now cloned a cDNA expressing the BP1 protein. Sequencing revealed that BP1 is a member of the homeobox gene family and belongs to the subfamily called Distal-less (DLX), genes important in early development. Further analysis showed that BP1 is an isoform of DLX4. BP1 protein has repressor function towards the beta-globin promoter, acting through the two beta-globin DNA silencers, demonstrated in transient transfection assays. Strong BP1 expression is restricted to placenta and kidney tissue, with no expression in 48 other human tissues. BP1 exhibits regulated expression in the human erythroid cell line MB-02, where its expression decreases upon induction of the beta-globin gene. BP1 is thus the first member of the DLX family with known DNA binding sites and a function in globin gene regulation.

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Published In

Mol Cell Biol

DOI

ISSN

0270-7306

Publication Date

April 2002

Volume

22

Issue

8

Start / End Page

2505 / 2514

Location

United States

Related Subject Headings

  • Transcription Factors
  • Tissue Distribution
  • Sequence Homology, Amino Acid
  • Repressor Proteins
  • Protein Isoforms
  • Promoter Regions, Genetic
  • Pregnancy
  • Placenta
  • Oncogene Proteins
  • Molecular Sequence Data
 

Citation

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Chase, M. B., Fu, S., Haga, S. B., Davenport, G., Stevenson, H., Do, K., … Berg, P. E. (2002). BP1, a homeodomain-containing isoform of DLX4, represses the beta-globin gene. Mol Cell Biol, 22(8), 2505–2514. https://doi.org/10.1128/MCB.22.8.2505-2514.2002
Chase, Michael B., Sidong Fu, Susanne B. Haga, Gregory Davenport, Holly Stevenson, Khanh Do, Doris Morgan, Alex L. Mah, and Patricia E. Berg. “BP1, a homeodomain-containing isoform of DLX4, represses the beta-globin gene.Mol Cell Biol 22, no. 8 (April 2002): 2505–14. https://doi.org/10.1128/MCB.22.8.2505-2514.2002.
Chase MB, Fu S, Haga SB, Davenport G, Stevenson H, Do K, et al. BP1, a homeodomain-containing isoform of DLX4, represses the beta-globin gene. Mol Cell Biol. 2002 Apr;22(8):2505–14.
Chase, Michael B., et al. “BP1, a homeodomain-containing isoform of DLX4, represses the beta-globin gene.Mol Cell Biol, vol. 22, no. 8, Apr. 2002, pp. 2505–14. Pubmed, doi:10.1128/MCB.22.8.2505-2514.2002.
Chase MB, Fu S, Haga SB, Davenport G, Stevenson H, Do K, Morgan D, Mah AL, Berg PE. BP1, a homeodomain-containing isoform of DLX4, represses the beta-globin gene. Mol Cell Biol. 2002 Apr;22(8):2505–2514.

Published In

Mol Cell Biol

DOI

ISSN

0270-7306

Publication Date

April 2002

Volume

22

Issue

8

Start / End Page

2505 / 2514

Location

United States

Related Subject Headings

  • Transcription Factors
  • Tissue Distribution
  • Sequence Homology, Amino Acid
  • Repressor Proteins
  • Protein Isoforms
  • Promoter Regions, Genetic
  • Pregnancy
  • Placenta
  • Oncogene Proteins
  • Molecular Sequence Data