A5047488175- Genomics and Chromatin Dynamics
- Reproductive System and Pregnancy
- RNA Research and Splicing
- Preterm Birth and Chorioamnionitis
- Chromosomal and Genetic Variations
- Pregnancy and preeclampsia studies
- Epigenetics and DNA Methylation
- Pluripotent Stem Cells Research
- Pregnancy-related medical research
- Animal Genetics and Reproduction
- Neonatal Respiratory Health Research
- Birth, Development, and Health
- Developmental Biology and Gene Regulation
- CRISPR and Genetic Engineering
- Neuroendocrine regulation and behavior
- Nuclear reactor physics and engineering
- Nuclear Physics and Applications
- Historical Studies on Reproduction, Gender, Health, and Societal Changes
- X-ray Diffraction in Crystallography
- History of Science and Medicine
- Cardiac Imaging and Diagnostics
- Medical History and Innovations
- RNA modifications and cancer
- Historical Psychiatry and Medical Practices
- Fatigue and fracture mechanics
University of Toronto
2015-2025
Canada Research Chairs
2022
Transcriptional enhancers are critical for maintaining cell-type–specific gene expression and driving cell fate changes during development. Highly transcribed genes often associated with a cluster of individual such as those found in locus control regions. Recently, these have been termed stretch or super-enhancers, which predicted to regulate identity genes. We employed CRISPR/Cas9-mediated deletion approach study the function several enhancer clusters (ECs) isolated mouse embryonic stem...
How distal regulatory elements control gene transcription and chromatin topology is not clearly defined, yet these processes are closely linked in lineage specification during development. Through allele-specific genome editing interaction analyses of the
The spatiotemporal configuration of genes with distal regulatory elements is believed to be crucial for transcriptional control, but full mechanistic understanding lacking. We combine simultaneous live tracking pairs genomic loci and nascent transcripts molecular dynamics simulations assess the Sox2 gene its enhancer. find that both exhibit more constrained mobility than control sequences due stalled cohesin at CCCTC-binding factor sites. Strikingly, enhancer becomes on firing, homogenizing...
The spatiotemporal configuration of genes with distal regulatory elements, and the impact chromatin mobility on transcription, remain unclear. Loop extrusion is an attractive model for bringing genetic elements together, but how this functionally interacts transcription also largely unknown. We combine live tracking genomic loci nascent transcripts molecular dynamics simulations to assess 4D arrangement
During gestation, uterine smooth muscle cells transition from a state of quiescence to one contractility, but the molecular mechanisms underlying this at genomic level are not well-known. To better understand these events, we evaluated epigenetic landscape mouse myometrium during pregnant, laboring, and postpartum stages. We generated gestational time point–specific enrichment profiles for histone H3 acetylation on lysine residue 27 (H3K27ac), trimethylation 4 (H3K4me3), RNA polymerase II...
Abstract Sex-determining region Y box 2 (Sox2) is a critical transcription factor for embryogenesis and neural stem progenitor cell (NSPC) maintenance. While distal enhancers control Sox2 in embryonic cells (ESCs), closer to the gene are implicated transcriptional regulation development. We hypothesize that downstream enhancer cluster, termed regulatory regions 2-18 (SRR2-18), regulates we investigate this NSPCs derived from mouse ESCs. Using functional genomics CRISPR-Cas9 mediated deletion...
Spontaneous uterine contractions are initiated when smooth muscle cells (SMCs) within the muscle, or myometrium, transition from a functionally dormant to an actively contractile phenotype at end of pregnancy period. We know that this process is accompanied by gestational time point-specific differences in SMC transcriptome, which can be modulated activator protein 1 (AP-1), nuclear factor kappa beta (NF-κβ), estrogen receptor (ER), and progesterone (PR) transcription factors. Less known,...
The spatiotemporal configuration of genes with distal regulatory elements, and the impact chromatin mobility on transcription, remain unclear. Loop extrusion is an attractive model for bringing genetic elements together, but how this functionally interacts transcription also largely unknown. We combine live tracking genomic loci nascent transcripts molecular dynamics simulations to assess arrangement Sox2 gene its enhancer, in response a battery perturbations. find close link between...
The uterine muscular layer, or myometrium, undergoes profound changes in global gene expression during its progression from a quiescent state pregnancy to contractile at the onset of labor. In this study, we investigate role SOX family transcription factors myometrial cells and provide evidence for SOX4 regulating labor-associated genes. We show that Sox4 has elevated murine myometrium term laboring process two mouse models preterm Additionally, differentially affects promoter activity...
SUMMARY How distal regulatory elements control gene transcription and chromatin topology is not clearly defined, yet these processes are closely linked in lineage specification during development. Through allele-specific genome editing interaction analyses of the Sox2 locus mouse embryonic stem cells, we found a striking disconnection between transcriptional architecture. We trace nearly all activation to small number key factor binding sites, whose deletions have no effect on...
Abstract During gestation, uterine smooth muscle cells transition from a state of quiescence to one contractility, but the molecular mechanisms underlying this at genomic level are not well-known. To better understand these events, we evaluated epigenetic landscape mouse myometrium during pregnancy, labor and post-partum. We established gestational timepoint-specific enrichment profiles involving histone H3K27 acetylation (H3K27ac), H3K4 tri-methylation (H3K4me3), RNA polymerase II (RNAPII)...
Abstract Embryonic development depends on spatially and temporally orchestrated gene regulatory networks. Expressed in neural stem progenitor cells (NSPCs), the transcription factor sex-determining region Y box 2 (Sox2) is critical for embryogenesis cell maintenance development. Whereas Sox2 regulated by a distal cluster of enhancers embryonic (ESCs), closer to have been implicated transcriptional regulation lineage. Using functional genomics data, deletion analysis we show that downstream...
Abstract The uterine muscular layer, or myometrium, undergoes profound changes in global gene expression during its progression from a quiescent state pregnancy to contractile at the onset of labor. In this study, we investigate role SOX family transcription factors myometrial cells and provide evidence for SOX4 regulating labor-associated genes. We show that Sox4 has elevated murine myometrium term laboring process two mouse models preterm Additionally, differentially affects promoter...
John Wiltshire, Frances Burney and the Doctors: Patient Narratives Then Now (Cambridge: Cambridge University Press, 2019), pp. 212, £75.00, hardback/e-book, ISBN: 9781108476362/9781108754361. - Volume 64 Issue 4
This article offers a critical reading of the representational prevalence paternal eye in British eighteenth-century depictions breastfeeding. I demonstrate how Romantic period embraced concept father’s gaze as physiologically intuitive and culturally significant form participation nursing act, one deemed necessary for both infant spousal well-being. Tracing its evolving ideological legacy from William Cadogan’s foundational An Essay upon Nursing (1748) to late works, particularly texts...
Abstract Spontaneous uterine contractions are initiated when smooth muscle cells (SMCs) within the muscle, or myometrium, transition from a functionally dormant to an actively contractile phenotype at end of pregnancy period. We know that this process is accompanied by gestational time point-specific differences in SMC transcriptome, which can be modulated Activator protein 1 (AP-1), Nuclear factor kappa beta (Nf-κβ), Estrogen receptor (ER), and Progesterone (PR) transcription factors. Less...