Identification of a negative regulatory DNA element for neuronal BC1 RNA expression by RNA polymerase III

Biochim Biophys Acta. 2000 Sep 7;1493(1-2):142-50. doi: 10.1016/s0167-4781(00)00175-5.

Abstract

BC1 RNA is a neuronal cell-specific RNA polymerase III (Pol III) transcript. The BC1 RNA gene has plural types of Pol III promoters, in addition to which an E-box sequence (E2 site) acts as a transcriptional activator, which is recognized by a brain-specific protein(s). Using an in vitro transcription system, we found that the upstream region of the BC1 RNA gene contained a sequence that interfered with the activity of the E-box element in a distance-independent manner. A tandem repeat within this sequence, which was weakly homologous with the neuron-restrictive silencer element (NRSE) found in the Pol II system, was recognized by a brain nuclear protein. Consistently, the transcriptional activity increased by deleting the tandem repeat sequence. We called this BC1 RNA-repressing element BCRE. The DNA-binding specificities of BCRE-binding protein differed from that of NRSE-binding protein (NRSF). A similar protein with an ability to bind to BCRE was also found in liver and kidney. Furthermore, the glutamate analog kainic acid increased the DNA-binding of both E2 site-binding protein and BCRE-binding protein, and then the levels of BC1 RNA also increased transiently. Our results suggested that both positive and negative regulatory elements contribute to neuronal BC1 RNA expression.

MeSH terms

  • Animals
  • Base Sequence
  • Brain / metabolism*
  • DNA-Binding Proteins / chemistry
  • DNA-Binding Proteins / metabolism*
  • Down-Regulation
  • Gene Expression Regulation
  • Kainic Acid
  • Male
  • Mice
  • Mice, Inbred ICR
  • Plasmids
  • RNA Polymerase III / genetics
  • RNA Polymerase III / metabolism*
  • RNA, Small Cytoplasmic / antagonists & inhibitors
  • RNA, Small Cytoplasmic / biosynthesis*
  • RNA, Small Cytoplasmic / genetics
  • Rats
  • Rats, Wistar
  • Seizures / chemically induced
  • Seizures / metabolism
  • Transcription, Genetic

Substances

  • BC1 RNA
  • DNA-Binding Proteins
  • RNA, Small Cytoplasmic
  • RNA Polymerase III
  • Kainic Acid