Document 0607
 DOCN  M9550607
 TI    Repetitive Alu elements form a cruciform structure that regulates the
       function of the human CD8 alpha T cell-specific enhancer.
 DT    9505
 AU    Hanke JH; Hambor JE; Kavathas P; Department of Molecular Genetics and
       Protein Chemistry, Pfizer; Central Research, Groton, CT 06340.
 SO    J Mol Biol. 1995 Feb 10;246(1):63-73. Unique Identifier : AIDSLINE
       MED/95156490
 AB    We previously identified a T cell-specific enhancer in the last intron
       of the human CD8 alpha gene that is adjacent to a sequence element that
       significantly represses enhancer function. This negative regulatory
       region consists of a half-Alu sequence that has potential to base-pair
       with a downstream Alu element, which is part of the fully active
       enhancer, to form a cruciform structure. The activity of this half-Alu
       silencer sequence is position and orientation-dependent, suggesting that
       DNA structure plays an important role in its function. Using
       site-directed mutational analysis and P1 nuclease mapping, we directly
       demonstrate that formation of a cruciform structure is required for
       repression of enhancer function in transient transfection assays.
       Finally, a P1 nuclease-sensitive site is present in the endogenous CD8
       alpha gene in T cell lines providing indirect evidence that the
       stem-loop may form in vivo. Taken together, these results suggest that
       Alu elements may contribute to the regulation of the CD8 alpha gene
       enhancer through the formation of secondary structure that disrupts
       enhancer function.
 DE    Aspergillus Nuclease S1  Base Sequence  Cell Line  Chromatin/METABOLISM
       CD8-Positive T-Lymphocytes/*PHYSIOLOGY  DNA Mutational Analysis  DNA,
       Single-Stranded/METABOLISM  Enhancer Elements (Genetics)/*GENETICS
       Human  Introns/GENETICS  Molecular Sequence Data  *Nucleic Acid
       Conformation  Plasmids/CHEMISTRY  Repetitive Sequences, Nucleic
       Acid/*GENETICS  Sequence Deletion/PHYSIOLOGY  Support, Non-U.S. Gov't
       Support, U.S. Gov't, P.H.S.  JOURNAL ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).