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DR1  -  down-regulator of transcription 1, TBP...

Gallus gallus

 
 
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Disease relevance of DR1

  • To clarify the sequence requirements for plus-strand primer cleavage and translocation, we have constructed mutants of the duck hepatitis B virus bearing base changes in or around the DR1 sequence in the primer [1].
 

High impact information on DR1

  • Nested deletion and mutagenesis studies show that a conserved DR1 element within the 135-bp proximal MTP promoter is responsible for differential expression by L35 and FAO cells [2].
  • The initial product of reverse transcription, minus-strand DNA, contains two copies of a short direct repeat (DR) sequence, termed DR1 and DR2 [1].
  • A point mutation at the terminal nucleotide of DR1 has a striking phenotype: normal levels of duplex viral DNA are produced, but nearly all of the DNA is linear rather than circular [1].
  • One is a direct repeat separated by one nucleotide DR1 (-146- TGGACTtAGTTCA-134) and the other is a direct repeat separated by five nucleotides DR5 (-139-AGTTCAaggccGGG TAA-123) [3].
  • The orphan nuclear receptor, hepatocyte nuclear factor 4 (HNF-4)1, binds to the DR1 sequence as assessed by electrophoretic mobility shift assay, and activates the CYP7A promoter/reporter activity by about 9-fold [3].
 

Biological context of DR1

  • We have examined the consequences on duck hepatitis B virus DNA synthesis of deleting the 5' and 3' copies of the 12 base sequence, DR1, from the viral pregenome [4].
  • Moreover, transient transfection studies reveal its capability to transactivate canonical DR1, DR4, and DR5 sequences and the constitutive activity of cTR2 is mapped to the N-terminal region of this orphan receptor [5].

References

  1. Mutations affecting hepadnavirus plus-strand DNA synthesis dissociate primer cleavage from translocation and reveal the origin of linear viral DNA. Staprans, S., Loeb, D.D., Ganem, D. J. Virol. (1991) [Pubmed]
  2. ARP-1/COUP-TF II determines hepatoma phenotype by acting as both a transcriptional repressor of microsomal triglyceride transfer protein and an inducer of CYP7A1. Kang, S., Spann, N.J., Hui, T.Y., Davis, R.A. J. Biol. Chem. (2003) [Pubmed]
  3. Transcriptional activation of the cholesterol 7alpha-hydroxylase gene (CYP7A) by nuclear hormone receptors. Crestani, M., Sadeghpour, A., Stroup, D., Galli, G., Chiang, J.Y. J. Lipid Res. (1998) [Pubmed]
  4. Replication of DHBV genomes with mutations at the sites of initiation of minus- and plus-strand DNA synthesis. Condreay, L.D., Wu, T.T., Aldrich, C.E., Delaney, M.A., Summers, J., Seeger, C., Mason, W.S. Virology (1992) [Pubmed]
  5. Molecular cloning and characterization of chicken orphan nuclear receptor cTR2. Sanyal, S., Handschin, C., Podvinec, M., Song, K.H., Kim, H.J., Kim, J.Y., Seo, Y.W., Kim, S.A., Kwon, H.B., Lee, K., Kim, W.S., Meyer, U.A., Choi, H.S. Gen. Comp. Endocrinol. (2003) [Pubmed]
 
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