Binding preferences of the POU domain protein Brain-4: implications for autoregulation.
The POU domain-containing transcription factor Brain-4 (Brn-4, RHS-2) was examined for its sites of expression and DNA binding preferences. In the rat, Brn-4 is expressed in 76 and 65% of vasopressin neurons in the paraventricular and supraoptic nuclei, respectively; but in only 10% of corticotropin-releasing factor neurons in the paraventricular nucleus of the hypothalamus. From these data we speculate that genes expressed within vasopressinergic neurons are more likely to be regulated by Brn-4 than those in corticotropin-releasing factor neurons. Random oligonucleotide site selection indicates Brn-4 prefers binding the DNA element CAATATGCTAAT and is inflexible in its spacing requirement between putative CAATAT and TAAT half sites, preferring 2 nucleotides between these elements. Electrophoretic mobility shift and DNase I footprinting analyses show five regions between nucleotides -457 and +22 of the Brn-4 promoter that are bound by Brn-4. Furthermore, Brn-4 can transactivate from this region of the Brn-4 promoter, suggesting that Brn-4 expression may be autoregulated.
Malik
K F
KF
Laboratory of Cell Biology, NIMH, NIH, Bethesda, MD 20892, USA. kmalik@codon.nih.gov
Kim
J
J
Hartman
A L
AL
Kim
P
P
Young
W S
WS
D000225:Adenine / Q000737:chemistry; D000818:Animals; D018983:DNA Footprinting; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000502:physiology*; D006651:Histocytochemistry; D006706:Homeostasis; D017403:In Situ Hybridization; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000378:metabolism*; D050809:POU Domain Factors; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D051381:Rats; D017207:Rats, Sprague-Dawley; D013941:Thymine / Q000737:chemistry; D014157:Transcription Factors / Q000737:chemistry / Q000378:metabolism*
D004268:DNA-Binding Proteins; D009419:Nerve Tissue Proteins; D050809:POU Domain Factors; C484088:Pou3f4 protein, rat; D014157:Transcription Factors; C074067:Pou3f4 protein, mouse; D000225:Adenine; D013941:Thymine