Proteomics

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The CRTC-1 transcriptional domain is required for COMPASS complex mediated longevity in C. elegans


ABSTRACT: Loss of function during ageing is accompanied by transcriptional drift, altering gene expression and contributing to a variety of age-related diseases. CREB-regulated transcriptional coactivators (CRTCs) have emerged as key regulators of gene expression that might be targeted to promote longevity. Here, we define the role of the Caenorhabditis elegans CRTC-1 in the epigenetic regulation of longevity. Endogenous CRTC-1 binds chromatin factors, including components of the COMPASS complex, which trimethylates lysine 4 on histone H3 (H3K4me3). CRISPR editing of endogenous CRTC-1 reveals that the CREB-binding domain in neurons is specifically required for H3K4me3-dependent longevity. However, this effect is independent of CREB but instead acts via the transcription factor AP-1. Strikingly, CRTC-1 also mediates global histone acetylation levels, and this acetylation is essential for H3K4me3-dependent longevity. Indeed, overexpression of an acetyltransferase enzyme is sufficient to promote longevity in wild-type worms. CRTCs, therefore, link energetics to longevity by critically fine-tuning histone acetylation and methylation to promote healthy ageing.

ORGANISM(S): Caenorhabditis Elegans

SUBMITTER: William B. Mair 

PROVIDER: PXD045674 | JPOST Repository | Tue Sep 26 00:00:00 BST 2023

REPOSITORIES: jPOST

Dataset's files

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20200312_N2_01.raw Raw
20200312_N2_02.raw Raw
20200312_N2_03.raw Raw
20200312_N2_04.raw Raw
20200312_WBM1241_01.raw Raw
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