A5073071237- Epigenetics and DNA Methylation
- Genomics and Chromatin Dynamics
- Cancer-related gene regulation
- RNA modifications and cancer
- Genetics and Neurodevelopmental Disorders
- Chromosomal and Genetic Variations
- Histone Deacetylase Inhibitors Research
- Pluripotent Stem Cells Research
- Chromatin Remodeling and Cancer
- Renal and related cancers
- Autism Spectrum Disorder Research
- Cancer Genomics and Diagnostics
- RNA Research and Splicing
- Cancer Cells and Metastasis
- Ubiquitin and proteasome pathways
- Peroxisome Proliferator-Activated Receptors
- Metal-Catalyzed Oxygenation Mechanisms
- RNA Interference and Gene Delivery
- Protein Degradation and Inhibitors
- Advanced biosensing and bioanalysis techniques
- Immune Cell Function and Interaction
- Prenatal Screening and Diagnostics
- Cancer, Hypoxia, and Metabolism
- Food Drying and Modeling
- Microbial Metabolic Engineering and Bioproduction
University of Oxford
2015-2024
University of California, San Francisco
2023
Ludwig Cancer Research
2011
John Radcliffe Hospital
2011
Genomics England
2008
University of Edinburgh
2003-2008
University of North Carolina at Chapel Hill
2006-2007
Howard Hughes Medical Institute
2006-2007
UNC Lineberger Comprehensive Cancer Center
2006
Wellcome Centre for Cell Biology
2004-2006
Chromatin modifying activities inherent to polycomb repressive complexes PRC1 and PRC2 play an essential role in gene regulation, cellular differentiation, development. However, the mechanisms by which these recognize their target sites function together form chromatin domains remain poorly understood. Recruitment of has been proposed occur through a hierarchical process, dependent on prior nucleation placement H3K27me3. Here, using de novo targeting assay mouse embryonic stem cells we...
CpG islands (CGIs) are associated with most mammalian gene promoters. A subset of CGIs act as polycomb response elements (PREs) and recognized by the silencing systems to regulate expression genes involved in early development. How function mechanistically nucleation sites for repressive complexes remains unknown. Here we discover that KDM2B (FBXL10) specifically recognizes non-methylated DNA recruits complex 1 (PRC1). This contributes histone H2A lysine 119 ubiquitylation (H2AK119ub1)...
The mechanisms by which the major Polycomb group (PcG) complexes PRC1 and PRC2 are recruited to target sites in vertebrate cells not well understood. Building on recent studies that determined a reciprocal relationship between DNA methylation activity, we demonstrate that, methylation-deficient embryonic stem (ESCs), CpG density combined with antagonistic effects of H3K9me3 H3K36me3 redirects PcG pericentric heterochromatin gene-rich domains. Surprisingly, find PRC1-linked H2A...
In higher eukaryotes, up to 70% of genes have high levels nonmethylated cytosine/guanine base pairs (CpGs) surrounding promoters and gene regulatory units. These features, called CpG islands, were identified over 20 years ago, but there remains little mechanistic evidence suggest how these enigmatic elements contribute promoter function, except that they are refractory epigenetic silencing by DNA methylation. Here we show islands directly recruit the H3K36-specific lysine demethylase enzyme...
Pioneer transcription factors recognise and bind their target sequences in inaccessible chromatin to establish new transcriptional networks throughout development cellular reprogramming. During this process, pioneer an accessible state facilitate additional factor binding, yet it remains unclear how different achieve this. Here, we discover that the pluripotency-associated OCT4 binds shape accessibility, co-binding, regulatory element function mouse embryonic stem cells. Chromatin...
The Polycomb system modifies chromatin and plays an essential role in repressing gene expression to control normal mammalian development. However, the components mechanisms that define how protein complexes achieve this remain enigmatic. Here, we use combinatorial genetic perturbation coupled with quantitative genomics discover central determinants of Polycomb-mediated repression mouse embryonic stem cells. We demonstrate canonical repressive complex 1 (PRC1), which mediates higher-order...
Two-thirds of gene promoters in mammals are associated with regions non-methylated DNA, called CpG islands (CGIs), which counteract the repressive effects DNA methylation on chromatin. In cold-blooded vertebrates, computational CGI predictions often reside away from promoters, suggesting a major divergence promoter architecture across vertebrates. By experimentally identifying genomes seven diverse we instead reveal that (NMIs) central feature vertebrate promoters. Furthermore, NMIs present...
The Polycomb repressive system is an essential chromatin-based regulator of gene expression. Despite being extensively studied, how the selects its target genes poorly understood, and whether histone-modifying activities are required for transcriptional repression remains controversial. Here, we directly test requirement PRC1 catalytic activity in function. To achieve this, develop a conditional mutation embryonic stem cells that completely removes activity. Using this system, demonstrate...
Chromatin landscapes are disrupted during DNA replication and must be restored faithfully to maintain genome regulation cell identity. The histone H3-H4 modification landscape is by parental recycling of new histones. How impacts on H2A-H2B currently unknown. Here, we measure modifications H2A.Z across the cycle using quantitative genomics. We show that H2AK119ub1, H2BK120ub1, recycled accurately replication. Modified segregated symmetrically daughter strands via POLA1 lagging strand, but...