Dataset Information

DVE-1 is telomere-binding protein and links the NuRD complex to telomere regulation in C.elegans

ABSTRACT: Telomeres comprise repetitive DNA sequences bound by specialized proteins at the end of linear chromosomes. Although some proteins have been identified and characterized in the nematode Caenorhabditis elegans, additional remain to be discovered, validated, and characterized. In our previous quantitative proteomics screen for telomere-binding proteins of C. elegans, we identified several candidates. One of these candidates was the homeobox protein DVE-1, a homolog of mammalian SATB proteins and transcription factor that plays a central role in the mitochondrial unfolded protein response. In this study, we validate DVE-1 as a telomere-binding protein in C. elegans. We show in vitro binding of DVE-1 to telomeric sequences and in vivo co-localization with the known telomere binding protein POT-1. Further, these results are supported by findings of DVE-1 ChIPseq analysis and RNA interference experiments followed by transcriptome and proteome analysis. Finally, we identified all core members of the nucleosome remodeling and deacetylase (NuRD) complex by DVE-1 immunoprecipitation and subsequent mass spectrometry experiments and bring them in the context of telomere organization.

INSTRUMENT(S):

ORGANISM(S): Caenorhabditis Elegans

SUBMITTER: F Butter

LAB HEAD: Falk Butter

PROVIDER: PXD069391 | Pride | 2026-06-15

REPOSITORIES: Pride

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			Action	DRS
	20231025_tims_FBU_JS_Proteome__dve1_L4440_1_Slot1-11_1_5518.d.zip	Other
	20231025_tims_FBU_JS_Proteome__dve1_L4440_2_Slot1-23_1_5520.d.zip	Other
	20231025_tims_FBU_JS_Proteome__dve1_L4440_3_Slot1-35_1_5522.d.zip	Other
	20231025_tims_FBU_JS_Proteome__dve1_L4440_4_Slot1-47_1_5524.d.zip	Other
	20231025_tims_FBU_JS_Proteome_dve-1RNAi_1_Slot1-59_1_5519.d.zip	Other

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Project description:Cellular senescence due to telomere dysfunction has been hypothesized to play a role in age-associated diseases including idiopathic pulmonary fibrosis (IPF). It has been postulated that paracrine mediators originating from senescent alveolar epithelia signal to surrounding mesenchymal cells and contribute to disease pathogenesis. However, murine models of telomere-induced alveolar epithelial senescence fail to display the canonical senescence-associated secretory phenotype (SASP) that is observed in senescent human cells. In an effort to understand human-specific responses to telomere dysfunction, we modelled telomere dysfunction-induced senescence in a human alveolar epithelial cell line. We hypothesized that this system would enable us to probe for differences in transcriptional and proteomic senescence pathways in vitro and to identify novel secreted protein (secretome) changes that potentially contribute to the pathogenesis of IPF. Following induction of telomere dysfunction, a robust senescence phenotype was observed. RNA-Seq analysis of the senescent cells revealed the SASP and comparisons to previous murine data highlighted species-specific responses to telomere dysfunction. We then conducted a proteomic analysis of the senescent cells using a novel biotin ligase capable of labeling secreted proteins. Candidate biomarkers selected from our transcriptional and secretome data were then evaluated in IPF and control patient plasma. Four novel proteins were found to be differentially expressed between the patient groups: stanniocalcin-1, contactin-1, tenascin C, and total inhibin. Our data show that human telomere-induced, alveolar epithelial senescence results in a transcriptional SASP that is distinct from that seen in analogous murine cells. Our findings suggest that studies in animal models should be carefully validated given the species-specific responses to telomere dysfunction. We also describe a pragmatic approach for the study of the consequences of telomere-induced alveolar epithelial cell senescence in humans.

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DVE-1 is telomere-binding protein and links the NuRD complex to telomere regulation in C.elegans

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