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Hagemann, L.

Publications and source records attributed to Hagemann, L..

2 recordsLinked to original sources

PWO1 and TRB proteins coordinate chromatin regulation to prevent premature differentiation and ectopic lignin deposition in Arabidopsis

The Arabidopsis PWWP-DOMAIN INTERACTOR OF POLYCOMBS1 (PWO1) and Telomere Repeat-Binding Proteins 1-3 (TRB1-3, TRBs) associate with distinct and shared protein complexes involved in epigenetic regulation, yet their cooperative roles in chromatin control and plant development remain largely unexplored. Here, we show that the interaction between PWO1 and TRBs is evolutionarily conserved. Both PWO1 and TRBs associate with plant telomeres, interact at these regions, and are co-enriched at subsets of interspersed telo-box motifs across regulatory regions genome-wide. TRBs facilitate PWO1 binding at shared genomic regions, including telo-box motifs. PWO1 and TRBs share a substantial number of genomic targets and preferentially bind chromatin regions associated with transcriptionally active states, whereas TRBs alone associate with repressive marks at thousands of loci. Genetic analyses show that the pwo1 trb1 trb3 triple mutant displays severe developmental defects, including main stem arrest and early maturation associated with aberrant lignin deposition in interfascicular tissues. In the triple mutant, key enzymes in the lignin biosynthesis pathway are upregulated, indicating that PWO1, TRB1, and TRB3 cooperatively regulate secondary cell wall formation. Together, our findings provide new insights into how PWO1 and TRBs cooperate to regulate chromatin states and orchestrate plant development, highlighting their central role in controlling gene expression programs. Significance statementThis study shows that PWO1 and TRB proteins co-occupy telomeres, including interspersed telo-box motifs, to regulate chromatin organization and plant development, particularly ectopic lignin deposition. Our findings reveal how these nuclear protein factors coordinate epigenetic states in Arabidopsis thaliana, providing a framework for understanding the control of developmental programs. O_FIG O_LINKSMALLFIG WIDTH=198 HEIGHT=200 SRC="FIGDIR/small/740627v1_ufig1.gif" ALT="Figure 1"> View larger version (38K): org.highwire.dtl.DTLVardef@1a3d544org.highwire.dtl.DTLVardef@1067082org.highwire.dtl.DTLVardef@1c49163org.highwire.dtl.DTLVardef@252171_HPS_FORMAT_FIGEXP M_FIG O_FLOATNOGraphical abstract:C_FLOATNO Evolutionarily conserved PWO-TRB interactions and their shared roles in chromatin regulation and plant development. Created with BioRender.com. C_FIG

plant biology↗

Platelet C5aR1 mediates sex-specific ischemia-driven revascularization through estradiol-dependent CXCL4 release

BackgroundSex-specific differences in cardiovascular diseases remain incompletely understood at the molecular level. ObjectivesHere, we investigated the role of the platelet complement receptor C5aR1 as a sex-specific critical mediator of revascularization following hindlimb ischemia. MethodsIschemia-driven revascularization was analyzed in the hind limb ischemia (HLI) model using wild type (WT) and complement receptor-deficient male and female mice, and involved mechanisms were analyzed in platelets and megakaryocyte-shed platelets ex vivo. ResultsIn WT mice, ischemic tissue exhibited robust complement activation with C3b and C5a accumulation that correlated strongly with deposition of the anti-angiogenic factor CXCL4 (PF4). Mechanistically, C5a stimulation of platelets triggered CXCL4 secretion, and female animals with a platelet-specific deletion of C5aR1 (using PF4-Cre-C5aR1fl/fl mice) showed a significantly delayed revascularization. Female mice exhibited substantially lower platelet C5aR1 expression, and C5a-induced CXCL4 secretion was virtually abolished compared to male animals. The sex-specific difference in tissue CXCL4 deposition was not present any more in the absence of C5aR1 from platelets. We observed that megakaryocytes, which give rise to platelets, express estradiol receptors. Importantly, estradiol stimulation of megakaryocytes suppressed C5aR1 expression during pro-platelet formation, uncovering a hormone-dependent regulatory mechanism. ConclusionsThe here described estradiol-C5aR1-CXCL4 axis provides a molecular explanation for sex-specific differences in ischemic revascularization known from patient studies. Our findings establish a novel and unexpected mechanistic link between sex hormones, a complement-platelet crosstalk and the angiogenic response to ischemia with potential clinical implications for sex-specific personalized therapeutic strategies.

immunology↗