Abstract
Retinoblastoma (pRb) is a multifunctional regulator, which was likely present in the last common ancestor of all eukaryotes. The Arabidopsis pRb homolog RETINOBLASTOMA RELATED 1 (RBR1), similar to its animal counterparts, controls not only cell proliferation but is also implicated in developmental decisions, stress responses and maintenance of genome integrity. Although most functions of pRb-type proteins involve chromatin association, a genome-wide understanding of RBR1 binding sites in Arabidopsis is still missing. Here, we present a plant chromatin immunoprecipitation protocol optimized for genome-wide studies of indirectly DNA-bound proteins like RBR1. Our analysis revealed binding of Arabidopsis RBR1 to approximately 1000 genes and roughly 500 transposable elements, preferentially MITES. The RBR1-decorated genes broadly overlap with previously identified targets of two major transcription factors controlling the cell cycle, i.e. E2F and MYB3R3 and represent a robust inventory of RBR1-targets in dividing cells. Consistently, enriched motifs in the RBR1-marked domains include sequences related to the E2F consensus site and the MSA-core element bound by MYB3R transcription factors. Following up a key role of RBR1 in DNA damage response, we performed a meta-analysis combining the information about the RBR1-binding sites with genome-wide expression studies under DNA stress. As a result, we present the identification and mutant characterization of three novel genes required for growth upon genotoxic stress.
Highlights
The first molecular function assigned to the human tumor suppressor Retinoblastoma was that of a transcriptional repressor controlling entry into S-phase
The Retinoblastoma tumor suppressor is a master regulator of the cell cycle and its inactivation is associated with many types of cancer
We describe here the first genome-wide DNA-binding study for a plant pRb protein, i.e. RETINOBLASTOMA RELATED 1 (RBR1), the only pRb homolog in Arabidopsis thaliana
Summary
The first molecular function assigned to the human tumor suppressor Retinoblastoma (pRb) was that of a transcriptional repressor controlling entry into S-phase. It was shown that pRb binds and inhibits the function of E2F-DP transcription factors and that phosphorylation of pRb by CDK-cyclin complexes disrupts this interaction, releasing E2F-controlled genes from repression [1]. A wealth of additional functions in cell proliferation, differentiation, environmental response and genome stability have been discovered for the family of pRb related proteins in various organisms [2,3,4,5]. More than 200 interactors of human pRb are listed in the BioGRID database [6], reflecting the multi-functionality of this molecular hub. In the model plant Arabidopsis thaliana, there is only one homolog, termed RBR1 (RETINOBLASTOMA RELATED 1) and its loss is female gametophytic lethal [11]
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