A5025844855- Pluripotent Stem Cells Research
- Genetics and Neurodevelopmental Disorders
- CRISPR and Genetic Engineering
- Genomic variations and chromosomal abnormalities
- 3D Printing in Biomedical Research
- RNA modifications and cancer
- Amino Acid Enzymes and Metabolism
- Ubiquitin and proteasome pathways
- Biomedical Ethics and Regulation
- Genomics and Chromatin Dynamics
- Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- Epigenetics and DNA Methylation
- Pancreatic function and diabetes
- Protein Degradation and Inhibitors
- DNA Repair Mechanisms
- Chromosomal and Genetic Variations
MRC Protein Phosphorylation and Ubiquitylation Unit
2020-2024
University of Dundee
2020-2024
Centro Andaluz de Biología Molecular y Medicina Regenerativa
2024
Universidad de Sevilla
2024
Universidad Pablo de Olavide
2024
Junta de Andalucía
2024
Medical Research Council
2022-2023
Abstract Deficiencies in the BRCA1 tumor suppressor gene are main cause of hereditary breast and ovarian cancer. is involved Homologous Recombination DNA repair pathway and, together with BARD1, forms a heterodimer ubiquitin E3 activity. The relevance BRCA1/BARD1 activity for suppression remains controversial. Here, we observe that not required or resistance to Olaparib. Using TULIP2 methodology, which enables direct identification E3-specific ubiquitination substrates, identify substrates...
Chromatin Immunoprecipitation (ChIP) and Co-Immunoprecipitation (CoIP) assays are the most common approaches to characterize genomic localization protein interactors, respectively, for a of interest. However, these require use specific antibodies, which costly reagents that often face sensitivity specificity issues. Based on TurboID, we developed PLAMseq (Proximity Labelled Affinity-purified Mass spectrometry plus sequencing), enables, in same workflow, identify loci interacting proteome...
The E3 ubiquitin ligase RNF12 plays essential roles during development, and the gene encoding it,
In female mice, the gene dosage from X chromosomes is adjusted by a process called chromosome inactivation (XCI) that occurs in two steps. An imprinted form of XCI (iXCI) silences paternally inherited (Xp) initiated at 2- to 4-cell stages. As extraembryonic cells including trophoblasts keep Xp silenced, epiblast give rise embryo proper reactivate and undergo random (rXCI) around implantation. Both iXCI rXCI require lncRNA Xist , which expressed be inactivated. The X-linked E3 ubiquitin...
Protein ubiquitylation regulates key biological processes including transcription. This is exemplified by the E3 ubiquitin ligase RNF12/RLIM, which controls developmental gene expression ubiquitylating REX1 transcription factor and mutated in an X-linked intellectual disability disorder. However, precise mechanisms drives specific transcriptional responses are not known. Here, we show that RNF12 recruited to genomic locations via a consensus sequence motif, enables co-localisation with...
Human induced pluripotent stem cells (hiPSCs) have great potential to be used as alternatives embryonic (hESCs) in regenerative medicine and disease modelling, thereby avoiding many of the ethical issues arising from use embryo-derived cells. However, despite clear similarities between two cell types, it is likely they are not identical. In this study, we characterise proteomes multiple hiPSC hESC lines derived independent donors. We find that while hESCs hiPSCs express a near identical set...
Tonne-Kalscheuer syndrome (TOKAS) is an X-linked intellectual disability associated with variable clinical features including craniofacial abnormalities, hypogenitalism and diaphragmatic hernia. TOKAS caused exclusively by variants in the gene encoding E3 ubiquitin ligase RLIM, also known as RNF12. Here we report identification of a novel RLIM missense variant, c.1262A>G p.(Tyr421Cys) adjacent to regulatory basic region, which causes severe form resulting perinatal lethality Inheritance...
Ubiquitylation enzymes are involved in all aspects of eukaryotic biology and frequently disrupted disease. One example is the E3 ubiquitin ligase RNF12/RLIM, which mutated developmental disorder Tønne-Kalscheuer syndrome (TOKAS). RNF12 TOKAS variants largely disrupt catalytic activity, presents a pressing need to develop approaches assess impact on activity patients. Here, we use photocrosslinking activity-based probes (photoABPs) monitor RING normal pathogenic contexts. We demonstrate that...
Human induced pluripotent stem cells (hiPSCs) have great potential to be used as alternatives embryonic (hESCs) in regenerative medicine and disease modelling. In this study, we characterise the proteomes of multiple hiPSC hESC lines derived from independent donors find that while they express a near-identical set proteins, show consistent quantitative differences abundance subset proteins. hiPSCs increased total protein content, maintaining comparable cell cycle profile hESCs, with...
Human induced pluripotent stem cells (hiPSCs) have great potential to be used as alternatives embryonic (hESCs) in regenerative medicine and disease modelling, thereby avoiding ethical issues arising from the use of embryo-derived cells. However, despite clear similarities between two cell types, it is likely they are not identical. In this study we characterise proteomes multiple hiPSC hESC lines derived independent donors. We find that while hESCs hiPSCs express a near identical set...
Human induced pluripotent stem cells (hiPSCs) have great potential to be used as alternatives embryonic (hESCs) in regenerative medicine and disease modelling. In this study, we characterise the proteomes of multiple hiPSC hESC lines derived from independent donors find that while they express a near-identical set proteins, show consistent quantitative differences abundance subset proteins. hiPSCs increased total protein content, maintaining comparable cell cycle profile hESCs, with...
Summary The E3 ubiquitin ligase RNF12/RLIM controls developmental gene expression and is mutated in the X-linked intellectual disability disorder Tonne-Kalscheuer syndrome (TOKAS). However, mechanisms by which RNF12 activity specific signatures are not known. Here, we show that chromatin forms a regulatory platform for substrate ubiquitylation transcriptional patterning. recruited to genomic regions via distinct consensus sequence motif, enables targeting key transcription factor REX1....
ABSTRACT Tonne-Kalscheuer syndrome (TOKAS) is an X-linked intellectual disability associated with variable clinical features including craniofacial abnormalities, hypogenitalism and diaphragmatic hernia. TOKAS caused exclusively by variants in the gene encoding E3 ubiquitin ligase RLIM , also known as. Here we report identification of a novel missense variant, c.1262A>G p.(Tyr421Cys) adjacent to regulatory basic region, which causes severe form resulting perinatal lethality Inheritance...
Summary In female mice the gene dosage from X chromosomes is adjusted by a process called chromosome inactivation (XCI) that occurs in two steps. An imprinted form of XCI (iXCI) silencing paternally inherited (Xp) initiated at 2-4 cell stages. As extraembryonic cells including trophoblasts keep Xp silenced, epiblast give rise to embryo proper reactivate and undergo random (rXCI) during peri-implantation Lack compensation leads lethality due inhibition trophoblast stem cells. However, as...
Abstract Human induced pluripotent stem cells (hiPSCs) have great potential to be used as alternatives embryonic (hESCs) in regenerative medicine and disease modelling, thereby avoiding many of the ethical issues arising from use embryo-derived cells. However, despite clear similarities between two cell types, it is likely they are not identical. In this study, we characterise proteomes multiple hiPSC hESC lines derived independent donors. We find that while hESCs hiPSCs express a near...