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Sci Rep. 2017 Jul 7;7(1):4845. doi: 10.1038/s41598-017-04936-7.

Nuclear receptors connect progenitor transcription factors to cell cycle control.

Author information

1
CABD, Andalusian Centre for Developmental Biology, CSIC-UPO-JA, 41013, Seville, Spain.
2
i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Rua Alfredo Allen, 208, 4200-135, Porto, Portugal.
3
IBMC - Instituto de Biologia Molecular e Celular, Universidade do Porto, Rua Alfredo Allen, 208, 4200-135, Porto, Portugal.
4
School of Medicine, University of Leuven, box 602 3000, Leuven, Belgium.
5
Department of Medical Biology L2-109, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
6
School of Medicine, University of Leuven, box 602 3000, Leuven, Belgium. stein.aerts@kuleuven.vib.be.
7
CABD, Andalusian Centre for Developmental Biology, CSIC-UPO-JA, 41013, Seville, Spain. fcasfer@upo.es.

Abstract

The specification and growth of organs is controlled simultaneously by networks of transcription factors. While the connection between these transcription factors with fate determinants is increasingly clear, how they establish the link with the cell cycle is far less understood. Here we investigate this link in the developing Drosophila eye, where two transcription factors, the MEIS1 homologue hth and the Zn-finger tsh, synergize to stimulate the proliferation of naïve eye progenitors. Experiments combining transcriptomics, open-chromatin profiling, motif analysis and functional assays indicate that these progenitor transcription factors exert a global regulation of the proliferation program. Rather than directly regulating cell cycle genes, they control proliferation through an intermediary layer of nuclear receptors of the ecdysone/estrogen-signaling pathway. This regulatory subnetwork between hth, tsh and nuclear receptors might be conserved from Drosophila to mammals, as we find a significant co-overexpression of their human homologues in specific cancer types.

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