Embryonic stem cell biology and development are regulated by epigenetic mechanisms of gene expression involving chromatin modifying enzymes that promote DNA and histone modifications. We utilize embryonic stem cells (ESCs), induced pluripotent stem cells (iPSCs) and mice as model systems to study how these enzymes reshape the epigenome and control gene expression programs to regulate stem cell biology and embryogenesis. The lab specializes in advanced technologies in genome editing and generating complex mouse strains. We integrate genetic, cellular, molecular, biochemical and bioinformatics approaches to dissect epigenetic pathways and mechanisms in stem cells, during development and in diseases.
The Tet family of enzymes (Tet1/2/3) modify the DNA base 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC) and promote DNA demethylation and gene expression. They are abundant in various cell types including the zygote, ESCs, germ cells, hematopoietic stem cells (HSCs) and neurons. Over the years, our work in the field has defined key functions of Tet enzymes in ESC differentiation, germ cell reprogramming and development (Cell Stem Cell 2011, Developmental Cell 2013, Developmental Cell 2014, Cell Reports 2019) as well as in hematopoietic stem cells (HSCs) and malignancies (Nature Immunology 2015, Cell Reports 2015, Cell Reports 2019), and in memory extinction (Neuron 2013). Recently in my lab:
- We have shown that the biological roles of Tet enzymes go beyond their enzymatic activity in DNA demethylation. Such non-canonical functions present a novel layer of epigenetic regulation. We study their role in ESC pluripotency and development, as well as in HSCs and hematologic malignancies.
- We have established that Tet enzymes regulate lineage specification and organogenesis. We research their biologically critical functions in post gastrulation development.
- We have found that the DNA binding proteins, Rinf and Idax, partner with Tet enzymes and pluripotency factors in ESCs. We study how they target Tet enzymes and pluripotency factors to gene regulatory regions and control transcription in ESCs and during differentiation.
- We explore the base 5hmC and its derivatives as independent epigenetic marks. We study their involvement in regulation of gene expression during development and in onset of diseases.
Our research investigates novel biological roles of DNA modifying enzymes in regulation of stem cell biology, development and cancer. This line of research will unveil new mechanisms of epigenetic regulation by Tets/5hmC, and can lead to identification of unique markers and targets in stem cell applications and for treatment of diseases.
For more details on our research please visit our lab website: https://www.dawlatylaboratory.com