Overexpression of transcription factor BACH1 in fetal Down syndrome brain.
There is a series of about 12 transcription factors expressed on chromosome 21. These transcription factors (TFs) are major candidates for playing a pathogenetic role for the abnormal wiring of the brain in fetal Down Syndrome (DS) as approximately 5,000 TFs are developmentally involved in the complex architecture of the human brain. TF derangement in DS has been already reported and we decided to contribute to the problem by studying four TFs encoded on chromosome 21 in fetal DS brain. We used fetal cortex of 8 DS fetuses and 6 controls (females) from the 18-19th week of gestation. Brain homogenates were subject to immunoblotting using goat-anti-BACH1, rabbit anti-heme oxygenase 1 (HO1), rabbit anti-ERG, rabbit anti-RUNX1 and goat anti-SIM2 l. Antibodies against beta-actin were used to normalise cell loss and antibodies against neuron-specific enolase were used to compensate neuronal loss. BACH1 was significantly overexpressed in fetal DS (p < 0.008) as compared to controls whereas RUNX1 and ERG proteins were comparable between groups, and SIM2 l was not detectable in any specimen. BACH1 was even significantly increased in the DS panel when normalised versus the housekeeping protein beta-actin (p < 0.01) or the neuron specific enolase (p < 0.01). HO-1 was found comparable between groups. BACH1, a member of the family of BTB-basic leucine zipper transcription factors, regulates gene expression through the NF-E2 site. More specifically, BACH1 suppresses expression of HO1. Increased BACH1, however, did not lead to decreased HO1, which would have explained oxidative stress observed in fetal DS.
Ferrando-Miguel
R
R
Department of Pediatrics, University of Vienna, Austria.
Cheon
M S
MS
Yang
J W
JW
Lubec
G
G
D050976:Basic-Leucine Zipper Transcription Factors; D002540:Cerebral Cortex / Q000378:metabolism*; D004314:Down Syndrome / Q000235:genetics / Q000378:metabolism*; D051856:Fanconi Anemia Complementation Group Proteins; D005260:Female; D005333:Fetus / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental / Q000502:physiology; D006801:Humans; D018709:Statistics, Nonparametric; D014157:Transcription Factors / Q000096:biosynthesis* / Q000235:genetics
C102108:BACH1 protein, human; D050976:Basic-Leucine Zipper Transcription Factors; D051856:Fanconi Anemia Complementation Group Proteins; D014157:Transcription Factors