Overexpression of transcription factor BACH1 in fetal Down Syndrome brain

  • R. Ferrando-Miguel
  • M. S. Cheon
  • J.-W. Yang
  • G. Lubec
Part of the Journal of Neural Transmission Supplement 67 book series (NEURAL SUPPL, volume 67)


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 1 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.


Bacterial Artificial Chromosome Down Syndrome Fetal Brain Neuron Specific Enolase Gene Dosage Effect 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



Down Syndrome




Transcription regulation protein BTB and CNC homolog 1


heme oxygenase 1


Single-minded homolog 2


Runt-related transcription factor 1


Neuron specific enolase


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Copyright information

© Springer-Verlag 2003

Authors and Affiliations

  • R. Ferrando-Miguel
    • 1
  • M. S. Cheon
    • 1
  • J.-W. Yang
    • 1
  • G. Lubec
    • 1
    • 2
  1. 1.Department of PediatricsUniversity of ViennaAustria
  2. 2.CChem, FRSC (UK), Department of PediatricsUniversity of ViennaViennaAustria

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