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Your search keyword '"Cuartero, S"' showing total 3 results
Start Over Author "Cuartero, S" Topic chromatin
3 results on '"Cuartero, S"'

1. CEBPA phase separation links transcriptional activity and 3D chromatin hubs.

Author

Christou-Kent M, Cuartero S, Garcia-Cabau C, Ruehle J, Naderi J, Erber J, Neguembor MV, Plana-Carmona M, Alcoverro-Bertran M, De Andres-Aguayo L, Klonizakis A, Julià-Vilella E, Lynch C, Serrano M, Hnisz D, Salvatella X, Graf T, and Stik G

Subjects
Cell Nucleus, Macrophages, Chromatin, Gene Expression Regulation
Abstract

Cell identity is orchestrated through an interplay between transcription factor (TF) action and genome architecture. The mechanisms used by TFs to shape three-dimensional (3D) genome organization remain incompletely understood. Here we present evidence that the lineage-instructive TF CEBPA drives extensive chromatin compartment switching and promotes the formation of long-range chromatin hubs during induced B cell-to-macrophage transdifferentiation. Mechanistically, we find that the intrinsically disordered region (IDR) of CEBPA undergoes in vitro phase separation (PS) dependent on aromatic residues. Both overexpressing B cells and native CEBPA-expressing cell types such as primary granulocyte-macrophage progenitors, liver cells, and trophectoderm cells reveal nuclear CEBPA foci and long-range 3D chromatin hubs at CEBPA-bound regions. In short, we show that CEBPA can undergo PS through its IDR, which may underlie in vivo foci formation and suggest a potential role of PS in regulating CEBPA function., Competing Interests: Declaration of interests D.H. and X.S. are scientific founders and advisors of Nuage Therapeutics., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Published
2023
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2. Three-dimensional genome organization in immune cell fate and function.

Author

Cuartero S, Stik G, and Stadhouders R

Subjects
Humans, Cell Differentiation genetics, Genome, Chromatin genetics, Chromosomes
Abstract

Immune cell development and activation demand the precise and coordinated control of transcriptional programmes. Three-dimensional (3D) organization of the genome has emerged as an important regulator of chromatin state, transcriptional activity and cell identity by facilitating or impeding long-range genomic interactions among regulatory elements and genes. Chromatin folding thus enables cell type-specific and stimulus-specific transcriptional responses to extracellular signals, which are essential for the control of immune cell fate, for inflammatory responses and for generating a diverse repertoire of antigen receptor specificities. Here, we review recent findings connecting 3D genome organization to the control of immune cell differentiation and function, and discuss how alterations in genome folding may lead to immune dysfunction and malignancy., (© 2022. Springer Nature Limited.)

Published
2023
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3. The Mutational Landscape of Myeloid Leukaemia in Down Syndrome

Author

de Castro, CPM, Cadefau, M, and Cuartero, S

Subjects
trisomy 21, myeloid leukaemia, Down syndrome, acute megakaryoblastic leukaemia (AMKL), chromatin, signalling, transcription
Abstract

Simple Summary Leukaemia occurs when specific mutations promote aberrant transcriptional and proliferation programs, which drive uncontrolled cell division and inhibit the cell's capacity to differentiate. In this review, we summarize the most frequent genetic lesions found in myeloid leukaemia of Down syndrome, a rare paediatric leukaemia specific to individuals with trisomy 21. The evolution of this disease follows a well-defined sequence of events and represents a unique model to understand how the ordered acquisition of mutations drives malignancy. Children with Down syndrome (DS) are particularly prone to haematopoietic disorders. Paediatric myeloid malignancies in DS occur at an unusually high frequency and generally follow a well-defined stepwise clinical evolution. First, the acquisition of mutations in the GATA1 transcription factor gives rise to a transient myeloproliferative disorder (TMD) in DS newborns. While this condition spontaneously resolves in most cases, some clones can acquire additional mutations, which trigger myeloid leukaemia of Down syndrome (ML-DS). These secondary mutations are predominantly found in chromatin and epigenetic regulators-such as cohesin, CTCF or EZH2-and in signalling mediators of the JAK/STAT and RAS pathways. Most of them are also found in non-DS myeloid malignancies, albeit at extremely different frequencies. Intriguingly, mutations in proteins involved in the three-dimensional organization of the genome are found in nearly 50% of cases. How the resulting mutant proteins cooperate with trisomy 21 and mutant GATA1 to promote ML-DS is not fully understood. In this review, we summarize and discuss current knowledge about the sequential acquisition of genomic alterations in ML-DS.

Published
2021

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