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Updated: Dec 21, 2025

In Vivo Functional Study of Disease-associated Rare Human Variants Using Drosophila
Published on: August 20, 2019
The role of SETD1A and SETD1B in development and disease
Andrea Kranz1, Konstantinos Anastassiadis2
1Genomics, Center for Molecular and Cellular Bioengineering, Biotechnology Center, Technische Universität Dresden, Tatzberg 47, 01307 Dresden, Germany.
Abstract:
The Trithorax-related Set1 H3K4 methyltransferases are conserved from yeast to human. In yeast loss of Set1 causes pleiotropic effects but is compatible with life. In contrast, both mammalian Set1 orthologs: SETD1A and SETD1B are essential for embryonic development, however they have distinct functions. SETD1A is required shortly after epiblast formation whereas SETD1B becomes indispensible during early organogenesis. In adult mice both SETD1A and SETD1B regulate hematopoiesis differently: SETD1A is required for the establishment of definitive hematopoiesis whereas SETD1B is important for the maintenance of long-term hematopoietic stem cells. Both are implicated in different diseases with accumulating evidence for the association of SETD1A variants in neurological disorders and SETD1B variants with cancer. Why the two paralogs cannot or only partially compensate for the loss of each other is part of the puzzle that we try to sort out in this review.
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