Genomics

Dataset Information

0

ACSS2 and ACLY link nutrient-dependent chromatin accessibility to regulation of CD8 T cell effector responses


ABSTRACT: Coordination of cellular metabolism is essential for optimal T cell responses. Here, we identify cytosolic acetyl-CoA production as an essential metabolic node for CD8 T cell function in vivo. We show that acetyl-CoA derived from mitochondrial citrate via the enzyme ATP citrate lyase (Acly) is required for CD8 T cell responses to infection. However, ablation of Acly triggers an alternative, acetate-dependent pathway for acetyl-CoA production in T cells mediated by acyl-CoA synthetase short chain family member 2 (Acss2). Mechanistically, acetate fuels both the TCA cycle and cytosolic acetyl-CoA production, impacting T cell effector responses, acetate-dependent histone acetylation, and effector gene expression by altering chromatin accessibility. When Acly is functional, Acss2 is not required, suggesting acetate is not an obligate metabolic substrate for CD8 T cell function. However, deletion of Acly renders CD8 T cells dependent on acetate (via Acss2) to maintain acetyl-CoA production and effector function. Thus, together Acly and Acss2 coordinate cytosolic acetyl-CoA production in CD8 T cells to maintain chromatin accessibility and T cell effector function.

ORGANISM(S): Mus musculus

PROVIDER: GSE262865 | GEO | 2024/08/01

REPOSITORIES: GEO

Dataset's files

Source:
Action DRS
Other
Items per page:
1 - 1 of 1

Similar Datasets

2024-07-04 | GSE270851 | GEO
2024-07-04 | GSE267377 | GEO
2024-07-29 | PXD054314 | Pride
2024-08-01 | GSE247358 | GEO
2023-05-10 | GSE223966 | GEO
2017-05-01 | E-GEOD-76853 | biostudies-arrayexpress
2022-09-25 | GSE137977 | GEO
2024-10-16 | GSE271035 | GEO
2023-05-04 | GSE202280 | GEO
2023-05-04 | GSE202279 | GEO