ORCID Profile
0000-0002-9053-4676
Current Organisations
Charles University
,
Charles University in Prague
,
Academy of Sciences of the Czech Republic
,
INSERM/UMR 7242
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Publisher: eLife Sciences Publications, Ltd
Date: 25-03-2014
DOI: 10.7554/ELIFE.01632
Abstract: Post-translational modifications of proteins have emerged as a major mechanism for regulating gene expression. However, our understanding of how histone modifications directly affect chromatin function remains limited. In this study, we investigate acetylation of histone H3 at lysine 64 (H3K64ac), a previously uncharacterized acetylation on the lateral surface of the histone octamer. We show that H3K64ac regulates nucleosome stability and facilitates nucleosome eviction and hence gene expression in vivo. In line with this, we demonstrate that H3K64ac is enriched in vivo at the transcriptional start sites of active genes and it defines transcriptionally active chromatin. Moreover, we find that the p300 co-activator acetylates H3K64, and consistent with a transcriptional activation function, H3K64ac opposes its repressive counterpart H3K64me3. Our findings reveal an important role for a histone modification within the nucleosome core as a regulator of chromatin function and they demonstrate that lateral surface modifications can define functionally opposing chromatin states.
Publisher: Elsevier BV
Date: 02-2019
Publisher: Springer Science and Business Media LLC
Date: 07-06-2018
DOI: 10.1038/S41467-018-04603-Z
Abstract: Cell growth and survival depend on a delicate balance between energy production and synthesis of metabolites. Here, we provide evidence that an alternative mitochondrial complex II (CII) assembly, designated as CII low , serves as a checkpoint for metabolite biosynthesis under bioenergetic stress, with cells suppressing their energy utilization by modulating DNA synthesis and cell cycle progression. Depletion of CII low leads to an imbalance in energy utilization and metabolite synthesis, as evidenced by recovery of the de novo pyrimidine pathway and unlocking cell cycle arrest from the S-phase. In vitro experiments are further corroborated by analysis of paraganglioma tissues from patients with sporadic, SDHA and SDHB mutations. These findings suggest that CII low is a core complex inside mitochondria that provides homeostatic control of cellular metabolism depending on the availability of energy.
Location: Portugal
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for Silvia Magalhaes-Novais.