Sistema de Salut de Catalunya
Institut Català de la Salut
[Vezzoli M, Morselli M, Montanini B] Department of Chemistry, Life Sciences and Environmental Sustainability, University of Parma, Parma, Italy. [de Llobet Cucalon LI] Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. [Di Vona C] Genome Biology Program, Center for Genomic Regulation (CRG), Barcelona Institute of Science and Technology (BIST) and Universitat Pompeu Fabra (UPF), Barcelona, Spain. CIBER of Rare Diseases (CIBERER), Barcelona, Spain. [de la Luna S] Genome Biology Program, Center for Genomic Regulation (CRG), Barcelona Institute of Science and Technology (BIST) and Universitat Pompeu Fabra (UPF), Barcelona, Spain. CIBER of Rare Diseases (CIBERER), Barcelona, Spain. Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Spain
Vall d'Hebron Barcelona Hospital Campus
2023-03-10T08:56:11Z
2023-03-10T08:56:11Z
2023-02-11
Acetylation; Neurogenesis
Acetilación; Neurogénesis
Acetilació; Neurogènesi
Regulation of histone acetylation dictates patterns of gene expression and hence cell identity. Due to their clinical relevance in cancer biology, understanding how human embryonic stem cells (hESCs) regulate their genomic patterns of histone acetylation is critical, but it remains largely to be investigated. Here, we provide evidence that acetylation of histone H3 lysine-18 (H3K18ac) and lysine-27 (H3K27ac) is only partially established by p300 in stem cells, while it represents the main histone acetyltransferase (HAT) for these marks in somatic cells. Our analysis reveals that whereas p300 marginally associated with H3K18ac and H3K27ac in hESCs, it largely overlapped with these histone marks upon differentiation. Interestingly, we show that H3K18ac is found at “stemness” genes enriched in RNA polymerase III transcription factor C (TFIIIC) in hESCs, whilst lacking p300. Moreover, TFIIIC was also found in the vicinity of genes involved in neuronal biology, although devoid of H3K18ac. Our data suggest a more complex pattern of HATs responsible for histone acetylations in hESCs than previously considered, suggesting a putative role for H3K18ac and TFIIIC in regulating “stemness” genes as well as genes associated with neuronal differentiation of hESCs. The results break ground for possible new paradigms for genome acetylation in hESCs that could lead to new avenues for therapeutic intervention in cancer and developmental diseases.
This work was supported by Bando Galileo 2022 (G22-142) to R.F. and M.T. The research is also supported by the AIRC IG Grant 27712-A to R.F. This work was also supported by the Spanish Ministry of Science and Innovation (PID2019-107185GB-I00) to S.d.l.L. The CRG acknowledge the support of the Spanish Ministry of Science and Innovation to the EMBL partnership, the Centro de Excelencia Severo Ochoa and the support of the CERCA Programme/Generalitat de Catalunya. This work was also supported by the Ligue Contre le Cancer, committees des Landes et de la Dordogne to M.T.
Article
Published version
English
Cèl·lules mare embrionàries; Epigènesi; Càncer - Tractament; PHENOMENA AND PROCESSES::Genetic Phenomena::Gene Expression Regulation::Epigenesis, Genetic; ANATOMY::Cells::Stem Cells::Pluripotent Stem Cells::Embryonic Stem Cells::Human Embryonic Stem Cells; DISEASES::Neoplasms; Other subheadings::Other subheadings::/therapy; FENÓMENOS Y PROCESOS::fenómenos genéticos::regulación de la expresión génica::epigénesis genética; ANATOMÍA::células::células madre::células madre pluripotentes::células madre embrionarias::células madre embrionarias humanas; ENFERMEDADES::neoplasias; Otros calificadores::Otros calificadores::/terapia
MDPI
International Journal of Molecular Sciences;24(4)
https://doi.org/10.3390/ijms24043624
Attribution 4.0 International
http://creativecommons.org/licenses/by/4.0/
