A5102864202- Genomics and Chromatin Dynamics
- Estrogen and related hormone effects
- RNA Research and Splicing
- PARP inhibition in cancer therapy
- Protein Degradation and Inhibitors
- Reproductive System and Pregnancy
- Cancer-related gene regulation
- Chromatin Remodeling and Cancer
- DNA Repair Mechanisms
- interferon and immune responses
- RNA modifications and cancer
- Cytokine Signaling Pathways and Interactions
- Microtubule and mitosis dynamics
- Epigenetics and DNA Methylation
- Hippo pathway signaling and YAP/TAZ
- RNA Interference and Gene Delivery
- 14-3-3 protein interactions
- Animal Genetics and Reproduction
- Plant Molecular Biology Research
- Biochemical and Molecular Research
- Immunotherapy and Immune Responses
- NF-κB Signaling Pathways
- Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- Cancer-related molecular mechanisms research
- Cancer Cells and Metastasis
Barcelona Institute for Science and Technology
2016-2024
Centre for Genomic Regulation
2011-2024
Universitat Pompeu Fabra
2009-2024
Philipps University of Marburg
2004
Key nuclear processes in eukaryotes, including DNA replication, repair, and gene regulation, require extensive chromatin remodeling catalyzed by energy-consuming enzymes. It remains unclear how the ATP demands of such are met response to rapid stimuli. We analyzed this question context massive regulation changes induced progestins breast cancer cells found that is generated cell nucleus via hydrolysis poly(ADP-ribose) ADP-ribose. In presence pyrophosphate, ADP-ribose used pyrophosphatase...
Eukaryotic gene regulation implies that transcription factors gain access to genomic information via poorly understood processes involving activation and targeting of kinases, histone-modifying enzymes, chromatin remodelers chromatin. Here we report progestin in breast cancer cells requires a rapid transient increase poly-(ADP)-ribose (PAR), accompanied by dramatic decrease cellular NAD could have broad implications cell physiology. This nuclear PARylation is mediated PAR polymerase PARP-1...
Gene regulation by external signals requires access of transcription factors to DNA sequences target genes, which is limited the compaction in chromatin. Although we have gained insight into how core histones and their modifications influence this process, role linker remains unclear. Here show that, within first minute progesterone action, a complex cooperation between different enzymes acting on chromatin mediates histone H1 displacement as requisite for gene induction cell proliferation....
A close chromatin conformation precludes gene expression in eukaryotic cells. Genes activated by external cues have to overcome this repressive state locally changing structure a more open state. Although much is known about hormonal activation, how basal repression of regulated genes targeted the correct sites throughout genome not well understood. Here we report that breast cancer cells, unliganded progesterone receptor (PR) binds genomic and targets complex containing HP1γ...
In breast cancer cells, some topologically associating domains (TADs) behave as hormonal gene regulation units, within which transcription is coordinately regulated in response to steroid hormones. Here we further describe that responsive TADs contain 20- 100-kb-long clusters of intermingled estrogen receptor (ESR1) and progesterone (PGR) binding sites, hereafter called hormone-control regions (HCRs). T47D identified more than 200 HCRs, are frequently bound by unliganded ESR1 PGR. These HCRs...
Steroid hormones regulate gene expression by interaction of their receptors with hormone responsive elements (HREs) and recruitment kinases, chromatin remodeling complexes, coregulators to target promoters. Here we show that in breast cancer cells the BAF, but not closely related PBAF complex, is required for progesterone induction several genes including MMTV, where it catalyzes localized displacement histones H2A H2B subsequent NF1 binding. PCAF also needed acetylates histone H3 at K14, an...
Abstract The glucocorticoid and progesterone receptors (GR PR) are closely related members of the steroid receptor family. Despite sharing similar structural functional characteristics; cognate hormones display very distinct physiological responses. In mammary epithelial cells, PR activation is associated with incidence progression breast cancer, whereas GR to growth suppression differentiation. their pharmacological relevance, only a few studies have compared activities in same system....
Estrogen (E2) and Progesterone (Pg), via their specific receptors (ERalpha PR), are major determinants in the development progression of endometrial carcinomas, However, precise mechanism action role other transcription factors involved not entirely clear. Using Ishikawa cancer cells, we report that E2 treatment exposes a set progestin-dependent PR binding sites which include both progestin target genes. ChIP-seq results from hormone-treated cells revealed non-random distribution PAX2...
Here, we report that in T47D breast cancer cells 50 pM progestin is sufficient to activate cell cycle entry and the progesterone gene expression program. At this concentration, equivalent blood levels found around menopause, receptor (PR) binds only 2800 genomic sites, which are accessible ATAC cleavage prior hormone exposure. These highly sites (HAs) surrounded by well-organized nucleosomes exhibit enhancer features, including estrogen alpha (ERα), higher FOXA1 BRD4 (bromodomain containing...
Steroid hormones induce transcription of their responsive genes by complex mechanisms including synergism between the hormone receptors and other factors. On mouse mammary tumor virus (MMTV) promoter progesterone induction is mediated reciprocal receptor (PR) ubiquitous factor nuclear 1 (NF1). PR binding mediates ATP-dependent displacement histone H2A H2B, enabling NF1 access to its target site. In minichromosomes assembled in vitro facilitates hormone-responsive elements (HREs) precluding...
Steroid receptors were classically described for regulating transcription by binding to target gene promoters. However, genome-wide studies reveal that steroid receptors-binding sites are mainly located at intragenic regions. To determine the role of these sites, we examined effect progestins on bcl-x gene, where only progesterone receptor-binding (PRbs) identified. We found in response hormone treatment, PR is recruited along with two histone acetyltransferases CREB-binding protein (CBP)...
Chromatin-associated RNAs (cRNAs) are a poorly characterized fraction of cellular that co-purify with chromatin. Their full complexity and the mechanisms regulating their packaging chromatin association remain understood. Here, we address these questions in Drosophila. We find cRNAs constitute heterogeneous group RNA species is abundant heterochromatic transcripts. show interact nuclear ribonucleoproteins (hnRNP) hrp36/hrp48 depletion linker histone dH1 impairs this interaction. induces...
How genes are repressed by steroid hormones remains a matter of debate, and several indirect mechanisms have been proposed. We found that the ligand-activated progesterone receptor recruits to promoter downregulated repressor complex composed HP1γ, lysine demethylase LSD1, histone deacetylases, coREST, RNA SRA, ATPase BRG1. BRG1 is needed for chromatin remodeling facilitates deposition linker variant H1.2, which compacts hinders polymerase loading transcription. Thus, hormone receptors can...
Abstract The cancer epigenome has been studied in cells cultured two-dimensional (2D) monolayers, but recent studies highlight the impact of extracellular matrix and three-dimensional (3D) environment on multiple cellular functions. Here, we report physical, biochemical, genomic differences between T47D breast 2D as 3D spheroids. Cells within spheroids exhibit a rounder nucleus with less accessible, more compacted chromatin, well altered expression ~2000 genes, majority which become...
Highlights – Hormonal gene regulation requires synthesis of PAR and its degradation to ADP-ribose by PARG is converted ATP in the cell nuclei hormone-activated NUDIX5/NUDT5 Blocking nuclear formation precludes hormone-induced chromatin remodeling, proliferation Summary Key processes eukaryotes including DNA replication or repair require extensive remodeling catalyzed energy consuming enzymes. How energetic demands such are ensured response rapid stimuli remains unclear. We have analyzed this...