A5058371574- Epigenetics and DNA Methylation
- Genetic Syndromes and Imprinting
- Prenatal Screening and Diagnostics
- Genomics and Chromatin Dynamics
- Microbial metabolism and enzyme function
- Estrogen and related hormone effects
- Glutathione Transferases and Polymorphisms
- Cancer-related gene regulation
- Renal and related cancers
- Angiogenesis and VEGF in Cancer
- RNA Research and Splicing
- HER2/EGFR in Cancer Research
- Congenital heart defects research
- Down syndrome and intellectual disability research
- Genetics and Neurodevelopmental Disorders
- Microtubule and mitosis dynamics
- Cell Adhesion Molecules Research
- Pluripotent Stem Cells Research
- DNA Repair Mechanisms
- Redox biology and oxidative stress
- Hedgehog Signaling Pathway Studies
- Escherichia coli research studies
- Photosynthetic Processes and Mechanisms
- Ethics and Legal Issues in Pediatric Healthcare
- Salmonella and Campylobacter epidemiology
Vall d'Hebron Institute of Oncology
2019-2024
University of Campania "Luigi Vanvitelli"
2020
Institute of Genetics and Biophysics
2008-2020
Centre for Genomic Regulation
2013-2019
Universitat Internacional de Catalunya
2017-2019
Barcelona Institute for Science and Technology
2017-2019
Hospital del Mar Research Institute
2017
Ferioli & Gianotti (Italy)
2017
Universitat Pompeu Fabra
2013
University of Naples Federico II
2008
SummaryThe maintenance of H3K9 and DNA methylation at imprinting control regions (ICRs) during early embryogenesis is key to the regulation imprinted genes. Here, we reveal that ZFP57, its cofactor KAP1, associated effectors bind selectively H3K9me3-bearing, DNA-methylated allele ICRs in ES cells. KAP1 deletion induces a loss heterochromatin marks ICRs, whereas deleting ZFP57 or DNMTs leads ICR demethylation. Accordingly, find with hemimethylated DNA-binding NP95. Finally, identify...
Differentially methylated regions (DMRs) are associated with many imprinted genes. In mice methylation at a DMR upstream of the H19 gene known as Imprint Control region (IC1) is acquired in male germline and influences status DMRs 100 kb away adjacent Insulin-like growth factor 2 (Igf2) through long-range interactions. humans, germline-derived or post-zygotically imprinting defects IC1 aberrant activation repression IGF2, resulting congenital disorders Beckwith-Wiedemann (BWS) Silver-Russell...
ZFP57 is necessary for maintaining repressive epigenetic modifications at Imprinting control regions (ICRs). In mouse embryonic stem cells (ESCs), binds ICRs (ICRBS) and many other loci (non-ICRBS). To address the role of on all its target sites, we performed high-throughput multi-locus analyses inbred hybrid ESC lines carrying different gene knockouts. By using an allele-specific RNA-seq approach, demonstrate that loss results in derepression imprinted allele multiple genes clusters. We...
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...
The parent of origin-dependent expression the IGF2 and H19 genes is controlled by imprinting centre 1 (IC1) consisting in a methylation-sensitive chromatin insulator. Deletions removing part IC1 have been found patients affected overgrowth- tumour-associated Beckwith–Wiedemann syndrome (BWS). These mutations result hypermethylation remaining region, loss IGF2/H19 fully penetrant BWS phenotype when maternally transmitted. We now report that 12 additional cases with similar clinical but showed...
Polo-like kinase 1 (PLK1) is a key regulator of cell division and overexpressed in many types human cancers. Compared to its well-characterized role mitosis, little known about PLK1 functions interphase. Here, we report that mediates estrogen receptor (ER)-regulated gene transcription breast cancer cells. interacts with ER recruited cis-elements on chromatin. PLK1-coactivated genes included classical target such as Ps2, Wisp2, Serpina3 were enriched developmental tumor-suppressive functions....
Autism spectrum disorders are early onset neurodevelopmental characterized by deficits in social communication and restricted repetitive behaviors, yet they quite heterogeneous terms of their genetic basis phenotypic manifestations. Recently, de novo pathogenic mutations DYRK1A, a chromosome 21 gene associated to neuropathological traits Down syndrome, have been identified patients presenting recognizable syndrome included the autism spectrum. These produce DYRK1A kinases with partial or...
Oxidation of H3 at lysine 4 (H3K4ox) by lysyl oxidase-like 2 (LOXL2) generates an modification with unknown physiological function. We find that LOXL2 and H3K4ox are higher in triple-negative breast cancer (TNBC) cell lines patient-derived xenografts (PDXs) than those from other subtypes. ChIP-seq revealed is located primarily heterochromatin, where it involved chromatin compaction. Knocking down reduces levels causes decompaction, resulting a sustained activation the DNA damage response...
CDK16 (also known as PCTAIRE1 or PCTK1) is an atypical member of the cyclin-dependent kinase (CDK) family that forms active complex with cyclin Y (CCNY). Although both proteins have been recently implicated in cancer pathogenesis, it still unclear how CDK16/CCNY exerts its biological activity. To understand network, we used complementary proteomic approaches to identify potential substrates this complex. We identified several candidates implicating cytoskeletal dynamics, and focused on...
Breast cancer prognosis and response to endocrine therapy strongly depends on the expression of estrogen progesterone receptors (ER PR, respectively). Although much is known about ERα gene (ESR1) regulation after hormonal stimulation, how it regulated in hormone-free condition not fully understood. We used ER-/PR-positive breast cells investigate role PR ESR1 absence hormones. show that binds low-methylated promoter maintains both DNA methylation locus hormone-deprived cells. Depletion...
The protein MucR from Brucella abortus has been described as a transcriptional regulator of many virulence genes. It is member the Ros/MucR family comprising proteins that control expression genes important for successful interaction α-proteobacteria with their eukaryotic hosts. Despite clear evidence role in repressing genes, no study carried out so far demonstrating direct this promoter its target gene babR encoding LuxR-like virB In study, we show first time ability to bind...
Oxidation of histone H3 at lysine 4 (H3K4ox) is catalyzed by lysyl oxidase homolog 2 (LOXL2). This modification enriched in heterochromatin triple‐negative breast cancer (TNBC) cells and has been linked to the maintenance compacted chromatin. However, molecular mechanism underlying this still unknown. Here, we show that LOXL2 interacts with RuvB‐Like 1 (RUVBL1), (RUVBL2), Actin‐like protein 6A (ACTL6A), DNA methyltransferase 1associated (DMAP1), a complex involved incorporation variant...
The embryonal renal cancer Wilms tumor (WT) accounts for 7% of all children’s malignancies. Its most frequent molecular defect is represented by DNA methylation abnormalities at the imprinted 11p15.5 region. Multiple alterations dictated chromosome copy-number variations have been recently demonstrated in adult cancers, raising question whether multiple loci were also affected WT. To address this issue, we analyzed and profiles 7 48 WT samples. results that occurred 35% cases, but they...
Histone modifications regulate chromatin structure, gene transcription, and other nuclear processes. Among the histone modifications, methylation has been considered to be a stable, irreversible process due slow turnover of methyl groups in chromatin. However, discovery three different classes lysine-specific demethylases—KDM1, Jumonji domain-containing demethylases, lysyl oxidase-like 2 protein—has drastically changed this view, suggesting role for dynamic biological process. In review, we...
Abstract Breast cancer prognosis and response to endocrine therapy strongly depends on the expression of estrogen progesterone receptors (ER PR, respectively). Although much is known about ER α gene ( ESR1 ) regulation after hormonal stimulation, how it regulated in hormone-free condition not fully understood. We used ER-/PR-positive breast cells investigate role PR absence hormones. show that binds low-methylated promoter maintains both DNA methylation locus hormone-deprived cells....
Abstract In breast cancer cells, topologically associating domains (TADs) behave as units of hormonal gene regulation with transcripts within hormone responsive TADs changing coordinately their expression in response to steroid hormones. Here we further described that contain 20-100 kb-long clusters intermingled estrogen receptor (ER) and progesterone (PR) binding sites, hereafter called Hormone-Control Regions (HCRs). We identified more than 200 HCRs, which are frequently bound by ER PR...
ABSTRACT Autism spectrum disorders are early onset neurodevelopmental characterized by deficits in social communication and restricted repetitive behaviors, yet they quite heterogeneous terms of their genetic basis phenotypic manifestations. Recently, de novo pathogenic mutations DYRK1A , a chromosome 21 gene associated to neuropathological traits Down syndrome, have been identified patients presenting recognizable syndrome included the autism spectrum. These produce kinases with partial or...
SUMMARY The histone modification of H3 oxidized at lysine 4 (H3K4ox) is catalyzed by lysyl oxidase–like 2 (LOXL2) and enriched in heterochromatin triple-negative breast cancer (TNBC) cells. Although H3K4ox has been linked to the maintenance compacted chromatin, molecular mechanism underlying this unknown. Here we show that read CRL4B complex, leading ubiquitination H2A through E3 ligase RBX1. Finally, interactions between RUVBL1/2 LOXL2 are involved incorporation variant H2A.Z, which plays...
Abstract Oxidation of H3 at lysine 4 (H3K4ox) by lysyl oxidase–like 2 (LOXL2) generates an modification with unknown physiological function. We find that LOXL2 and H3K4ox are higher in triple-negative breast cancer (TNBC) cell lines patient–derived xenographs (PDXs) than those from other subtypes. ChIP-seq revealed is located primarily heterochromatin, where it involved chromatin compaction. Knocking down reduces levels causes decompaction, resulting a sustained activation the DNA damage...