A5032963843- Epigenetics and DNA Methylation
- Genomics and Chromatin Dynamics
- Pluripotent Stem Cells Research
- CRISPR and Genetic Engineering
- Genetic Syndromes and Imprinting
- Genetics and Neurodevelopmental Disorders
- Chromatin Remodeling and Cancer
- Single-cell and spatial transcriptomics
- RNA Research and Splicing
- Renal and related cancers
- Reproductive Biology and Fertility
- Cancer-related gene regulation
- Prenatal Screening and Diagnostics
- Tissue Engineering and Regenerative Medicine
- Liver physiology and pathology
- Animal Genetics and Reproduction
- Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- Child and Adolescent Health
- Big Data Technologies and Applications
- Hematopoietic Stem Cell Transplantation
- Advanced Data Processing Techniques
- Educational Tools and Methods
- Protein Degradation and Inhibitors
- Mesenchymal stem cell research
- Plant Molecular Biology Research
Peter MacCallum Cancer Centre
2020-2025
The University of Melbourne
2020-2025
Babraham Institute
2015-2023
Cold Spring Harbor Laboratory
2012-2015
A.S. Watson (Netherlands)
2013
Centenary Institute
2009
Cancer cells frequently depend on chromatin regulatory activities to maintain a malignant phenotype. Here, we show that leukemia require the mammalian SWI/SNF remodeling complex for their survival and aberrant self-renewal potential. While Brg1, an ATPase subunit of SWI/SNF, is known suppress tumor formation in several cell types, found instead rely Brg1 support oncogenic transcriptional program, which includes Myc as one its key targets. To account this context-specific function, identify...
The molecular regulation of zygotic genome activation (ZGA) in mammals remains an exciting area research. Primed mouse embryonic stem cells contain a rare subset “2C-like” that are epigenetically and transcriptionally similar to the two-cell embryo thus represent vitro approximation for studying ZGA transcription regulation. Recently, factor Dux, expressed minor wave ZGA, was described activate many downstream transcripts. However, it unknown what upstream maternal factors initiate either...
Random autosomal monoallelic gene expression refers to the transcription of a from one two homologous alleles. We assessed dynamics during development through an allele-specific RNA-sequencing screen in clonal populations hybrid mouse embryonic stem cells (ESCs) and neural progenitor (NPCs). identified 67 376 inheritable random monoallelically expressed genes ESCs NPCs, respectively, 5.6-fold increase upon differentiation. Although DNA methylation nuclear positioning did not distinguish...
Long noncoding (lnc)RNAs have recently emerged as key regulators of gene expression. Here, we performed high-depth poly(A) + RNA sequencing across multiple clonal populations mouse embryonic stem cells (ESCs) and neural progenitor (NPCs) to comprehensively identify differentially regulated lncRNAs. We establish a biologically robust profile lncRNA expression in these two cell types further confirm that the majority lncRNAs are enriched nucleus. Applying weighted coexpression network...
Zygotic genome activation (ZGA) is an essential transcriptional event in embryonic development that coincides with extensive epigenetic reprogramming. Complex manipulation techniques and maternal stores of proteins preclude large-scale functional screens for ZGA regulators within early embryos. Here, we combined pooled CRISPR (CRISPRa) single-cell transcriptomics to identify ZGA-like transcription mouse stem cells, which serve as a tractable, vitro proxy Using multi-omics factor analysis...
The pluripotent nature of embryonic stem cells (ESC) is associated with a dynamic open chromatin state and an irregular nuclear shape. It has been postulated that the absence Lamin A/C contributes to these features. However, we show mouse ESCs express low, yet readily detectable, amounts at both RNA protein levels. Full-length transcripts isoforms were detected by q-PCR deep sequencing. Additionally, expression was validated in multiple primary established ESC lines immunoblotting using...
Abstract Background Bivalent chromatin is an exemplar of epigenetic plasticity. This co-occurrence active-associated H3K4me3 and inactive-associated H3K27me3 histone modifications on opposite tails the same nucleosome occurs predominantly at promoters that are poised for future transcriptional upregulation or terminal silencing. We know little dynamics, resolution, regulation this state outside embryonic stem cells where it was first described. partly due to technical challenges...
Female human induced pluripotent stem cells frequently undergo X-chromosome inactivation (XCI) erosion, marked by X-inactive specific transcript (XIST) RNA loss and partial reactivation of the inactive X (Xi). This overlooked phenomenon limits our understanding its impact on cell applications. Here, we show that XCI erosion is frequent heterogeneous, leading to several X-linked genes. These are primarily located short arm chromosome, particularly near escape genes within H3K27me3-enriched...
Embryonic regulators are often re-expressed in cancers, however the functional and molecular significance of this is not always understood. The epigenetic priming factors Developmental Pluripotency Associated 2 4 (DPPA2/4) have crucial roles early development implicated cancer pathogenesis. We reveal non-small cell lung (NSCLC), DPPA2/4 co-expression associated with poorly differentiated tumours, impaired patient outcomes accelerated vivo xenograft tumour growth. Proteomic analyses dimerise...
Reprogramming of somatic cells into induced Pluripotent Stem Cells (iPSCs) is a major leap towards personalised approaches to disease modelling and cell-replacement therapies. However, we still lack the ability fully control epigenetic status iPSCs, which hurdle for their downstream applications. Epigenetic fidelity can be tracked by genomic imprinting, phenomenon dependent on DNA methylation, frequently perturbed in iPSCs yet unknown reasons. To try understand causes underlying these...
Genomic imprinting is an epigenetic phenomenon leading to parental allele-specific expression. Dosage of imprinted genes crucial for normal development and its dysregulation accounts several human disorders. This unusual expression pattern mostly dictated by differences in DNA methylation between alleles at specific regulatory elements known as control regions (ICRs). Although approaches can be used inspection, we lack easy cost-effective method simultaneously measure multiple regions. Here,...
Zygotic genome activation (ZGA) represents the initiation of transcription following fertilisation. Despite its importance, we know little molecular events that initiate mammalian ZGA in vivo. Recent vitro studies mouse embryonic stem cells have revealed developmental pluripotency associated 2 and 4 (Dppa2/4) as key regulators ZGA-associated transcription. However, their roles initiating vivo remain unexplored. We reveal Dppa2/4 proteins are present nucleus at all stages preimplantation...
Abstract Zygotic genome activation (ZGA) in mice takes place two waves, a minor wave the one-cell embryo, and major at two-cell stage, both accompanied by global transcriptional epigenetic reprogramming. However, orchestration of these reprogramming events maternal factors deposited oocyte is not yet entirely understood. We others have recently shown that modifiers such as SMARCA5 (the main ATPase ISWI complexes) can initiate ZGA programme vitro . So far, role vivo has been addressed,...
Changes in the epigenetic landscape are a hallmark of aging that contributes to irreversible decline organismal fitness ultimately leading aging-related diseases.Epigenetic modifications regulate cellular memory processes genomic imprinting and X-chromosome inactivation (XCI) ensure monoallelic expression imprinted X-linked genes.Whether aging-associated changes affect maintenance XCI has not been comprehensively studied.Here, we investigate allele-specific transcriptional signatures brain,...