Published in Current opinion in genetics & development
Eukaryote genomes encode a surprisingly large number of noncoding transcripts. Around two-thirds of human transcribed loci do not encode protein, and many are intergenic and produce long (>200 nucleotides) noncoding RNAs (lncRNAs). Extensive analyses using comparative genomics and transcriptomics approaches have established that lncRNA sequence and...
Published in Current opinion in genetics & development
Microsatellite-expansion diseases are a class of neurological and neuromuscular disorders caused by the expansion of short stretches of repetitive DNA (e.g. GGGGCC, CAG, CTG …) within the human genome. Since their discovery 20 years ago, research into how microsatellites expansions cause disease has been examined using the model that these genes ar...
Published in Current Opinion in Genetics & Development
The DNA damage response (DDR) orchestrates DNA repair and halts cell cycle. If damage is not resolved, cells can enter into an irreversible state of proliferative arrest called cellular senescence. Organismal ageing in mammals is associated with accumulation of markers of cellular senescence and DDR persistence at telomeres. Since the vast majority...
Published in Current Opinion in Genetics & Development
Circadian rhythms are generated by an intrinsic cellular mechanism that controls a large array of physiological and metabolic processes. There is erosion in the robustness of circadian rhythms during aging, and disruption of the clock by genetic ablation of specific genes is associated with aging-related features. Importantly, environmental conditi...
Published in Current opinion in genetics & development
The eukaryotic genome exists in vivo at an equimolar ratio with histones, thus forming a polymer composed of DNA and histone proteins. Each nucleosomal unit in this polymer provides versatile capabilities and dynamic range. Substitutions of the individual components of the histone core with structurally distinct histone variants and covalent modifi...
Over the past twenty years, exciting developments in optical and molecular imaging approaches have allowed researchers to examine with unprecedented resolution the spatial organization of transcription sites in the nucleus. An attractive model that has developed from these studies is that active genes cluster to preformed transcription factories th...
Published in Current Opinion in Genetics & Development
The nuclear periphery has been implicated in gene regulation and it has been proposed that proximity to the nuclear lamina and inner nuclear membrane (INM) leads to gene repression. More recently, it appears that there is a correlation and interdependence between lamina associated domains (LADs), the epigenome and overall three-dimensional architec...
Published in Current opinion in genetics & development
Published in Proceedings of the National Academy of Sciences of the United States of America
Recent studies of genome-wide chromatin interactions have revealed that the human genome is partitioned into many self-associating topological domains. The boundary sequences between domains are enriched for binding sites of CTCC-binding factor (CTCF) and the cohesin complex, implicating these two factors in the establishment or maintenance of topo...
Published in Current Opinion in Genetics & Development
During development, the genome adopts specific chromatin states to establish and maintain functionally distinct cell types in a well-controlled environment. A select group of transcription factors have the ability to drive the transition of the genome from a pluripotent to a more specialized chromatin state. The same set of factors can be used as r...
