GSE100829 The  C. elegans ortholog of TDP-43 regulates the chromatin localization of the heterochromatin protein 1 homolog, HPL-2

Contributors : Tassa K Saldi   ; Patrick Gonzales ; Alfonso Garrido-Lecca ; Vishantie Dostal ; Christine M Roberts ; Lenoard Petrucelli ; Christopher D LinkSeries Type : Expression profiling by high throughput sequencing ; Genome binding/occupancy profiling by high throughput sequencing ; OtherOrganism : Caenorhabditis elegansTDP-1 is the  C. elegans ortholog of mammalian TDP-43, which is strongly implicated in the etiology of Frontotemporal Dementia (FTD) and Amyotrophic Lateral Sclerosis (ALS). We discovered that deletion of the tdp-1 gene results in enhanced transcriptional gene silencing leading to increased sensitivity to he ritable RNA interference (RNAi). As heritable RNAi in C. elegans depends on chromatin changes moderated by HPL-2, a homolog of heterochromatin protein 1 (HP1), we investigated the interaction of TDP-1 and HPL-2. We find that TDP-1 and HPL-2 interact directly, and loss of TDP-1 dramatically alters the chromatin association of HPL-2.   We have shown previously that deletion of the tdp-1 gene results in transcriptional alterations and the accumulation of double-stranded (ds) RNA. These molecular changes are replicated in an hpl-2 deletion strain, consistent with HPL-2 acting downstream of TDP-1 to modulate these aspects of RNA metabolism. Our observations identify novel mechanisms by which HP1 homologs can be recruited to chromatin, and by which nuclear depletion of human TDP-43 could lead to disease-relevant changes in RNA metabolism.

Source: GEO: Gene Expression Omnibus - May 17, 2018 Category: Genetics & Stem Cells Tags: Expression profiling by high throughput sequencing Genome binding/occupancy profiling by high throughput sequencing Other Caenorhabditis elegans Source Type: research