Jennifer A. Mitchell
Professor
Campus
St. George (downtown)
CSB Appointment
Full
Research Areas
Animal Biology, Bioinformatics / Computational Biology, Developmental Biology, Genetics / Genomics, Molecular Biology, Systems Biology
Education
Ph.D. University of Toronto
B.Sc. University of Waterloo
Titles and Honors
CIHR New Investigator
Dorothy Shoichet Women Faculty Award of Excellence 2016
Primary Undergraduate Department
Cell & Systems Biology
Graduate Programs
Cell & Systems Biology
Genome Biology and Bioinformatics
Academic or Administrative Appointments
Associate Chair, Research
Research Description
How does our genome regulate the process of development and cell-type specialisation? Specific genes are expressed at discrete times due to the activation or repression of DNA regulatory regions. Our research investigates how the genome functions in stem cells to regulate self-renewal and differentiation. We often think about transcription as occurring on a particular gene in a linear manner whereas the nucleus is a three dimension organelle into which the genome is folded and organised. Within this folded structure DNA regulatory sequences physically contact the genes they regulate forming tissue-specific chromatin loops. We use CRISPR Genome Editing, Molecular Biology and Cellular Imaging techniques combined with Genome-Wide Sequencing approaches and Bioinformatics analysis to investigate the mechanisms that underlie tissue-specific regulation of gene expression and genome folding. Our previous work has identified the enhancers that activate numerous genes in stem cells including a distal enhancer of the Sox2 transcription factor which is required to maintain the stem cell state. The work we do provides a deeper understanding of how our DNA makes us unique and predisposes us to particular diseases. Our work also identifies new ways to consider treating genetic diseases with CRISPR Genome or Epigenome Editing.
Contact Information
Office Phone: 416-978-6711
Office: RW519A
Lab: RW519
Lab Phone: 416-978-6715
Email
Mailing Address
Department of Cell & Systems Biology
University of Toronto
25 Harbord St.
Toronto, ON M5S 3G5
Canada
Recent News
Publications
2024
Transcription processes compete with loop extrusion to homogenize promoter and enhancer dynamics
Platania A, Erb C, Barbieri M, Molcrette B, Grandgirard E, de Kort MAC, Pomp W, Meaburn K, Taylor T, Shchuka VM, Kocanova S, Nazarova M, Oliveira GM, Mitchell JA, Soutoglou E, Lenstra TL, Molina N, Papantonis A, Bystricky K, Sexton T
2024, Science Advances, 10.1126/sciadv.adq0987
2023
Epigenetic reprogramming of a distal developmental enhancer cluster drives SOX2 overexpression in breast and lung adenocarcinoma
Abatti LE, Lado-Fernández P, Huynh L, Collado M, Hoffman M, Mitchell J
2023, Nucleic Acids Research, 10.1093/nar/gkad734
Enhancer–promoter interactions can bypass CTCF-mediated boundaries and contribute to phenotypic robustness
Chakraborty S, Kopitchinski N, Zuo Z, Eraso A, Awasthi P, Chari R, Mitra A, Tobias IC, Moorthy SD, Dale RK, Mitchell JA, Petros TJ, Rocha PP
2023, Nature Genetics, 10.1038/s41588-022-01295-6
MYB and ELF3 differentially modulate labor-inducing gene expression in myometrial cells
Asakura A, Shchuka VM, Khader N, Dorogin A, Shynlova O, Mitchell JA
2023, PLOS ONE, 10.1371/journal.pone.0271081
2022
Transcriptional regulation and chromatin architecture maintenance are decoupled functions at the Sox2 locus.
Taylor T, Sikorska N, Shchuka VM, Chahar S, Ji C, Macpherson NN, Moorthy SD, de Kort MAC, Mullany S, Khader N, Gillespie ZE, Langroudi L, Tobias IC, Lenstra TL, Mitchell JA, Sexton T
2022, Genes & development, 35710138
Histone macroH2A1 is a stronger regulator of hippocampal transcription and memory than macroH2A2 in mice
Singh G, Stefanelli G, Narkaj K, Brimble MA, Creighton SD, McLean TAB, Hall M, Mitchnick KA, Zakaria J, Phung T, Reda A, Leonetti AM, Monks A, Ianov L, Winters BD, Walters BJ, Davidoff AM, Mitchell JA, Zovkic IB
2022, Communications Biology, 10.1038/s42003-022-03435-4
2021
The recycling endosome protein Rab25 coordinates collective cell movements in the zebrafish surface epithelium.
Willoughby PM, Allen M, Yu J, Korytnikov R, Chen T, Liu Y, So I, Macpherson N, Mitchell JA, Fernandez-Gonzalez R, Bruce AE
2021, eLife, 10, 33755014
A flexible repertoire of transcription factor binding sites and a diversity threshold determines enhancer activity in embryonic stem cells
Singh G, Mullany S, Moorthy SD, Zhang R, Mehdi T, Tian R, Duncan AG, Moses AM, Mitchell JA
2021, Genome Research, 10.1101/gr.272468.120
Transcriptional control of parturition: insights from gene regulation studies in the myometrium
Khader N, Shchuka VM, Shynlova O, Mitchell JA
2021, Molecular Human Reproduction, 10.1093/molehr/gaab024
2020
Enhancer-gene rewiring in the pathogenesis of Quebec platelet disorder.
Liang M, Soomro A, Tasneem S, Abatti LE, Alizada A, Yuan X, Uusküla-Reimand L, Antounians L, Alvi SA, Paterson AD, Rivard GÉ, Scott IC, Mitchell JA, Hayward CPM, Wilson MD
2020, Blood, 136, 2679-2690, 32663239
Transcriptional enhancers: from prediction to functional assessment on a genome-wide scale
Tobias IC, Abatti LE, Moorthy SD, Mullany S, Taylor T, Khader N, Filice MA, Mitchell JA
2020, Genome, 10.1139/gen-2020-0104
The pregnant myometrium is epigenetically activated at contractility-driving gene loci prior to the onset of labor in mice
Rivera RM, Shchuka VM, Abatti LE, Hou H, Khader N, Dorogin A, Wilson MD, Shynlova O, Mitchell JA
2020, PLOS Biology, 10.1371/journal.pbio.3000710
Genes responsive to rapamycin and serum deprivation are clustered on chromosomes and undergo reorganization within local chromatin environments
Belak ZR, Pickering JA, Gillespie ZE, Audette G, Eramian M, Mitchell JA, Bridger JM, Kusalik A, Eskiw CH
2020, Biochemistry and Cell Biology, 10.1139/bcb-2019-0096
2019
KLF4 protein stability regulated by interaction with pluripotency transcription factors overrides transcriptional control.
Dhaliwal NK, Abatti LE, Mitchell JA
2019, Genes & development, 31221664
Pluripotency on Lockdown after Deletion of Three Transcription Regulators.
Mitchell JA
2019, Cell stem cell, 24, 681-683, 31051130
Variational Infinite Heterogeneous Mixture Model for Semi-supervised Clustering of Heart Enhancers.
Mehdi TF, Singh G, Mitchell JA, Moses AM
2019, Bioinformatics (Oxford, England), 30753279
2018
KLF4 Nuclear Export Requires ERK Activation and Initiates Exit from Naive Pluripotency.
Dhaliwal NK, Miri K, Davidson S, Tamim El Jarkass H, Mitchell JA
2018, Stem cell reports, 10, 1308-1323, 29526737
2016
Enhancers and super-enhancers have an equivalent regulatory role in embryonic stem cells through regulation of single or multiple genes.
Moorthy SD, Davidson S, Shchuka VM, Singh G, Malek-Gilani N, Langroudi L, Martchenko A, So V, Macpherson NN, Mitchell JA
2017, Genome research, 27, 246-258, 27895109
Generating CRISPR/Cas9 Mediated Monoallelic Deletions to Study Enhancer Function in Mouse Embryonic Stem Cells.
Moorthy SD, Mitchell JA
2016, Journal of visualized experiments : JoVE, e53552, 27078492
Nuclear RNA Isolation and Sequencing.
Dhaliwal NK, Mitchell JA
2016, Methods in molecular biology (Clifton, N.J.), 1402, 63-71, 26721484
2015
Concordance between RNA-sequencing data and DNA microarray data in transcriptome analysis of proliferative and quiescent fibroblasts.
Trost B, Moir CA, Gillespie ZE, Kusalik A, Mitchell JA, Eskiw CH
2015, Royal Society open science, 2, 150402, 26473061
Chromatin Dynamics in Lineage Commitment and Cellular Reprogramming
Shchuka VM, Malek-Gilani N, Singh G, Langroudi L, Dhaliwal NK, Moorthy SD, Davidson S, Macpherson NN, Mitchell JA
2015, Genes, 6, 641-61, 26193323
The pluripotent regulatory circuitry connecting promoters to their long-range interacting elements
Schoenfelder S, Furlan-Magaril M, Mifsud B, Tavares-Cadete F, Sugar R, Javierre BM, Nagano T, Katsman Y, Sakthidevi M, Wingett SW, Dimitrova E, Dimond A, Edelman LB, Elderkin S, Tabbada K, Darbo E, Andrews S, Herman B, Higgs A, LeProust E, Osborne CS, Mitchell JA, Luscombe NM, Fraser P
2015, Genome research, 25, 582-97, 25752748
Rapamycin reduces fibroblast proliferation without causing quiescence and induces STAT5A/B-mediated cytokine production.
Gillespie ZE, MacKay K, Sander M, Trost B, Dawicki W, Wickramarathna A, Gordon J, Eramian M, Kill IR, Bridger JM, Kusalik A, Mitchell JA, Eskiw CH
2015, Nucleus (Austin, Tex.), 6, 490-506, 26652669
2014
A Sox2 distal enhancer cluster regulates embryonic stem cell differentiation potential
Zhou HY, Katsman Y, Dhaliwal NK, Davidson S, Macpherson NN, Sakthidevi M, Collura F, Mitchell JA
2014, Genes & development, 28, 2699-711, 25512558
2013
Nuclear organization of RNA polymerase II transcription
Davidson S, Macpherson N, Mitchell JA
2013, Biochemistry and cell biology = Biochimie et biologie cellulaire, 91, 22-30, 23442138
2012
Upstream distal regulatory elements contact the Lmo2 promoter in mouse erythroid cells
Bhattacharya A, Chen CY, Ho S, Mitchell JA
2012, PloS one, 7, e52880, 23285212
Nuclear RNA sequencing of the mouse erythroid cell transcriptome
Mitchell JA, Clay I, Umlauf D, Chen CY, Moir CA, Eskiw CH, Schoenfelder S, Chakalova L, Nagano T, Fraser P
2012, PloS one, 7, e49274, 23209567
Sensitive detection of chromatin coassociations using enhanced chromosome conformation capture on chip
Sexton T, Kurukuti S, Mitchell JA, Umlauf D, Nagano T, Fraser P
2012, Nature protocols, 7, 1335-50, 22722369
Enhancer identification in mouse embryonic stem cells using integrative modeling of chromatin and genomic features
Chen CY, Morris Q, Mitchell JA
2012, BMC genomics, 13, 152, 22537144
2009
Preferential associations between co-regulated genes reveal a transcriptional interactome in erythroid cells
Schoenfelder S, Sexton T, Chakalova L, Cope NF, Horton A, Andrews S, Kurukuti S, Mitchell JA, Umlauf D, Dimitrova DS, Eskiw CH, Luo Y, Wei CL, Ruan Y, Bieker JJ, Fraser P
2010, Nature genetics, 42, 53-61, 20010836
2008
The Air noncoding RNA epigenetically silences transcription by targeting G9a to chromatin
Nagano T, Mitchell JA, Sanz LA, Pauler FM, Ferguson-Smith AC, Feil R, Fraser P
2008, Science (New York, N.Y.), 322, 1717-20, 18988810
Transcription factories are nuclear subcompartments that remain in the absence of transcription
Mitchell JA, Fraser P
2008, Genes & development, 22, 20-5, 18172162
2007
Myc dynamically and preferentially relocates to a transcription factory occupied by Igh
Osborne CS, Chakalova L, Mitchell JA, Horton A, Wood AL, Bolland DJ, Corcoran AE, Fraser P
2007, PLoS biology, 5, e192, 17622196
Intergenic transcription, cell-cycle and the developmentally regulated epigenetic profile of the human beta-globin locus
Miles J, Mitchell JA, Chakalova L, Goyenechea B, Osborne CS, O'Neill L, Tanimoto K, Engel JD, Fraser P
2007, PloS one, 2, e630, 17637845
2005
Replication and transcription: shaping the landscape of the genome
Chakalova L, Debrand E, Mitchell JA, Osborne CS, Fraser P
2005, Nature reviews. Genetics, 6, 669-77, 16094312
2004
Differential activation of the connexin 43 promoter by dimers of activator protein-1 transcription factors in myometrial cells
Mitchell JA, Lye SJ
2005, Endocrinology, 146, 2048-54, 15618352
Active genes dynamically colocalize to shared sites of ongoing transcription
Osborne CS, Chakalova L, Brown KE, Carter D, Horton A, Debrand E, Goyenechea B, Mitchell JA, Lopes S, Reik W, Fraser P
2004, Nature genetics, 36, 1065-71, 15361872
Mechanical stretch and progesterone differentially regulate activator protein-1 transcription factors in primary rat myometrial smooth muscle cells
Mitchell JA, Shynlova O, Langille BL, Lye SJ
2004, American journal of physiology. Endocrinology and metabolism, 287, E439-45, 15126239
2003
Progesterone and gravidity differentially regulate expression of extracellular matrix components in the pregnant rat myometrium
Shynlova O, Mitchell JA, Tsampalieros A, Langille BL, Lye SJ
2004, Biology of reproduction, 70, 986-92, 14645109
Parathyroid hormone-related protein treatment of pregnant rats delays the increase in connexin 43 and oxytocin receptor expression in the myometrium
Mitchell JA, Ting TC, Wong S, Mitchell BF, Lye SJ
2003, Biology of reproduction, 69, 556-62, 12700188