Saturday, 23rd June 2018

 Development and Regeneration

    Transcription factors and heterochromatin formation in Drosophila







Natalia Azpiazu









Research summary:

Early Drosophila embryo. a-b) Stained with anti-HP1 (red) and topro3 (blue) to stain the nuclei. c-d) Stained with anti-PH3 (green) and topro3 (blue). a, c) Wild type embryo. Nuclei divide synchronously inside the yolk. b, d) Embryo mutant for eyegone. The embryo shows a clear asynchrony in the early divisions.

Transcription factors are known to be proteins capable of binding to the DNA to regulate the transcription of downstream genes. They have been considered to be key players in the development of Drosophila melanogaster, as they act upstream of many gene regulatory cascades. They function by binding to the DNA in promotors and/or enhancers activating or repressing their target genes.  For many years, we have focused our attention in two different types of transcription factors: the Hox-TALE family of proteins Homothorax (hth)/Extradenticle (exd) and the Pax family of proteins Eyegone (eyg)/Twin of eyegone (toe). Both have homologs along the Animal Kingdom and many different functions have been described for them in Drosophila as well as in vertebrates. Some years ago we described for the first time an unexpected role for hth during  the early pre-blastodermic divisions in Drosophila. We were able to show that Hth binds to satellite sequences facilitating their transcription. This transcription is essential for constitutive heterochromatin formation, that is, for correct assembly of centromeres and telomeres.  In the absence of Hth, the rapid syncytial divisions do not occur properly. We were also able to show that Eyg/Toe, known transriptional repressors during Drosophila development, regulate their target gene wingless (wg) by forming a closed heterochromatin like structure in its eye-enhancer. In the past months it has been shown that many Pax family members are able to bind to satellite sequences in mouse culture cells. All together this results open new and exciting avenues in the mode of action of transcription factors during development that we are currently investigating at the cellular and molecular level.