I’m a 3rd year Ph.D student. I’m interested in studying the gene expression dynamics and transcription factor binding occupancy during stem cell differentiation and embryonic development. Mouse embryonic stem cells can be differentiated into either neuron progenitor cells or mesoderm (as well as endoderm) progenitor cells depending on different levels of cell signaling molecules (Iwafuchi-Doi et al, 2012; Gouti et al, 2014), which lead to differentiated binding site occupancy of master transcription factors. However, how chromosome structural change during cell lineage specification affects the binding of these transcription factors, and further their target gene expression, is not very well understood.
I’ve been working on transcription factor (TF) binding site occupancy in relation to spatial co-localization of TF binding sites of the same TF and between different TFs during the my Ph.D. These BSs co-localization are made possible by chromosome looping and the segregation of chromosome subcompartments (Rao et al., 2014). We combined computational simulations with Hi-C map analysis to show the quantitative relationship between TF binding site co-localization and binding site occupancy boost from ChIP-seq profiles. Our results revealed a previously unnoticed role of chromosome architecture in determining TF binding dynamics and occupancy.
Therefore, I hope to combine the knowledge of chromosome organization variation induced TF binding site occupancy change with the mouse embryonic stem cell system in the lab to gain a better understanding of the interplay between cell signaling, TF binding, and if possible, chromosome organization dynamics.
Iwafuchi-Doi M, Matsuda K, Murakami K, Niwa H, Tesar PJ, Aruga J, Matsuo I, Kondoh H. Transcriptional regulatory networks in epiblast cells and during anterior neural plate development as modeled in epiblast stem cells. Development. 2012 Nov;139(21):3926-37.
Gouti M, Tsakiridis A, Wymeersch FJ, Huang Y, Kleinjung J, Wilson V, Briscoe J. In vitro generation of neuromesodermal progenitors reveals distinct roles for wnt signalling in the specification of spinal cord and paraxial mesoderm identity. PLoS Biol. 2014 Aug 26;12(8):e1001937.
Lieberman-Aiden, E., Van Berkum, N.L., Williams, L., Imakaev, M., Ragoczy, T., Telling, A., Amit, I., Lajoie, B.R., Sabo, P.J., Dorschner, M.O. and Sandstrom, R., 2009. Comprehensive mapping of long-range interactions reveals folding principles of the human genome. Science, 326(5950), pp.289-293.
Rao, S.S., Huntley, M.H., Durand, N.C., Stamenova, E.K., Bochkov, I.D., Robinson, J.T., Sanborn, A.L., Machol, I., Omer, A.D., Lander, E.S. and Aiden, E.L., 2014. A 3D map of the human genome at kilobase resolution reveals principles of chromatin looping. Cell, 159(7), pp.1665-1680.