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A Balance of Yki/Sd Activator and E2F1/Sd Repressor Complexes Controls Cell Survival and Affects Organ Size.

ABSTRACT: The Hippo/Yki and RB/E2F pathways both regulate tissue growth by affecting cell proliferation and survival, but interactions between these parallel control systems are poorly defined. In this study, we demonstrate that interaction between Drosophila E2F1 and Sd disrupts Yki/Sd complex formation and thereby suppresses Yki target gene expression. RBF modifies these effects by reducing E2F1/Sd interaction. This regulation has significant effects on apoptosis, organ size, and progenitor cell proliferation. Using a combination of DamID-seq and RNA-seq, we identified a set of Yki targets that play a diversity of roles during development and are suppressed by E2F1. Further, we found that human E2F1 competes with YAP for TEAD1 binding, affecting YAP activity, indicating that this mode of cross-regulation is conserved. In sum, our study uncovers a previously unknown mechanism in which RBF and E2F1 modify Hippo signaling responses to modulate apoptosis, organ growth, and homeostasis.

SUBMITTER: Zhang P

PROVIDER: S-EPMC5722641 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature

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A Balance of Yki/Sd Activator and E2F1/Sd Repressor Complexes Controls Cell Survival and Affects Organ Size.

Zhang Peng P Pei Chunli C Wang Xi X Xiang Jinyi J Sun Bao-Fa BF Cheng Yongsheng Y Qi Xiaolong X Marchetti Marco M Xu Jia-Wei JW Sun Ying-Pu YP Edgar Bruce A BA Yuan Zengqiang Z

Developmental cell 20171201 5

The Hippo/Yki and RB/E2F pathways both regulate tissue growth by affecting cell proliferation and survival, but interactions between these parallel control systems are poorly defined. In this study, we demonstrate that interaction between Drosophila E2F1 and Sd disrupts Yki/Sd complex formation and thereby suppresses Yki target gene expression. RBF modifies these effects by reducing E2F1/Sd interaction. This regulation has significant effects on apoptosis, organ size, and progenitor cell prolife ...[more]

PMID: 29207260

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Project description:BackgroundThe YABBY (YAB) family of transcription factors participate in a diverse range of processes that include leaf and floral patterning, organ growth, and the control of shoot apical meristem organisation and activity. How these disparate functions are regulated is not clear, but based on interactions with the LEUNIG-class of co-repressors, it has been proposed that YABs act as transcriptional repressors. In the light of recent work showing that DNA-binding proteins associated with the yeast co-repressor TUP1 can also function as activators, we have examined the transcriptional activity of the YABs.ResultsOf the four Arabidopsis YABs tested in yeast, only FILAMENTOUS FLOWER (FIL) activated reporter gene expression. Similar analysis with Antirrhinum YABs identified the FIL ortholog GRAMINIFOLIA as an activator. Plant-based transactivation assays not only confirmed the potential of FIL to activate transcription, but also extended this property to the FIL paralog YABBY3 (YAB3). Subsequent transcriptomic analysis of lines expressing a steroid-inducible FIL protein revealed groups of genes that responded either positively or negatively to YAB induction. Included in the positively regulated group of genes were the polarity regulators KANADI1 (KAN1), AUXIN RESPONSE FACTOR 4 (ARF4) and ASYMMETRIC LEAVES1 (AS1). We also show that modifying FIL to function as an obligate repressor causes strong yab loss-of-function phenotypes.ConclusionsCollectively these data show that FIL functions as a transcriptional activator in plants and that this activity is involved in leaf patterning. Interestingly, our study also supports the idea that FIL can act as a repressor, as transcriptomic analysis identified negatively regulated FIL-response genes. To reconcile these observations, we propose that YABs are bifunctional transcription factors that participate in both positive and negative regulation. These findings fit a model of leaf development in which adaxial/abaxial patterning is maintained by a regulatory network consisting of positive feedback loops.

Dataset Information

A Balance of Yki/Sd Activator and E2F1/Sd Repressor Complexes Controls Cell Survival and Affects Organ Size.

Publications

A Balance of Yki/Sd Activator and E2F1/Sd Repressor Complexes Controls Cell Survival and Affects Organ Size.

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