A5072100133- Genomics and Chromatin Dynamics
- RNA Research and Splicing
- Cancer-related molecular mechanisms research
- MicroRNA in disease regulation
- RNA and protein synthesis mechanisms
- Epigenetics and DNA Methylation
- Pluripotent Stem Cells Research
- Chromosomal and Genetic Variations
- Erythrocyte Function and Pathophysiology
- Genetics, Aging, and Longevity in Model Organisms
- Plant Molecular Biology Research
- Fungal and yeast genetics research
- CRISPR and Genetic Engineering
- Cancer-related gene regulation
- RNA modifications and cancer
MRC Weatherall Institute of Molecular Medicine
2013-2021
University of Oxford
2013-2021
Medical Research Council
2017
Imperial College London
2011-2016
John Radcliffe Hospital
2013
Abstract Background Mammalian transcriptomes contain thousands of long noncoding RNAs (lncRNAs). Some lncRNAs originate from intragenic enhancers which, when active, behave as alternative promoters producing transcripts that are processed using the canonical signals their host gene. We have followed up this observation by analyzing intergenic to determine extent which they might also enhancers. Results integrated high-resolution maps transcriptional initiation and transcription annotate a...
The human genome contains ∼30,000 CpG islands (CGIs). While CGIs associated with promoters nearly always remain unmethylated, many of the ∼9,000 lying within gene bodies become methylated during development and differentiation. Both promoter intragenic may also abnormally as a result rearrangements in malignancy. epigenetic mechanisms by which some but others, same cell, unmethylated these situations are poorly understood. Analyzing specific loci using genome-wide analysis, we show that...
Recently, a handful of intergenic long noncoding RNAs (lncRNAs) have been shown to compete with mRNAs for binding miRNAs and contribute development disease. Beyond these reports, little is yet known the extent functional consequences miRNA-mediated regulation mRNA levels by lncRNAs. To gain further insight into lncRNA-mRNA crosstalk, we reanalyzed transcriptome-wide changes induced targeted knockdown over 100 lncRNA transcripts in mouse embryonic stem cells (mESCs). We predicted that, on...
Abstract Self-interacting chromatin domains encompass genes and their cis -regulatory elements; however, the three-dimensional form a domain takes, whether this relies on enhancer–promoter interactions, processes necessary to mediate formation maintenance of such domains, remain unclear. To examine these questions, here we use combination high-resolution chromosome conformation capture, non-denaturing fluorescence in situ hybridisation super-resolution imaging study 70 kb encompassing mouse...
Numerous developmentally regulated genes in mouse embryonic stem cells (ESCs) are marked by both active (H3K4me3)- and polycomb group (PcG)-mediated repressive (H3K27me3) histone modifications. This bivalent state is thought to be important for transcriptional poising, but the mechanisms that regulate remain incompletely understood. Examining contribution of microRNAs (miRNAs) regulation genes, we found miRNA biogenesis enzyme DICER was required binding PRC2 core components EZH2 SUZ12,...
A variety of self-interacting domains, defined at different levels resolution, have been described in mammalian genomes. These include Chromatin Compartments (A and B) 1 , Topologically Associated Domains (TADs) 2,3 contact domains 4,5 sub-TADs 6 insulated neighbourhoods 7 frequently interacting regions (FIREs) 8 . Whereas many studies found the organisation to be conserved across cell types 3 9 some do form a lineage-specific manner 6710 However, it is not clear what degree such...
Our understanding of biological processes in humans is often based on examination analogous other organisms. The nematode worm Caenorhabditis elegans has been a particularly valuable model, leading to Nobel prize winning discoveries development and genetics. Until recently, however, the not widely used as model study transcription due lack comprehensive catalogue its RNA transcripts. A recent by Chen et al. uses next-generation sequencing address this issue, mapping initiation sites C....