My project is a cool combination of several areas: epigenetics, gene regulation, developmental biology, and computational biology. I aim to investigate the contribution of DNA sequence to epigenetic regulation by Polycomb/Trithorax group proteins.
During development, a complex multicellular organism originates from a zygote which has to proliferate, differentiate, and make up the whole body. Since the genetic material is identical among the cells, all the specialized cells owe their differences to differential gene expression profiles. In addition to transcription factors, some changes in gene expression during development are accompanied by epigenetic modifications. Epigenetic regulation of gene expression allows the cells to maintain their specialized states.
The Polycomb/Trithorax groups of proteins are chromatin modifier complexes which can work antagonistically on several hundred developmentally important target genes (such as the Hox genes, master transcriptional regulators, and genes involved in signalling and proliferation), to maintain repressed (PcG) or active (TrxG) transcription states. There are cis-regulatory elements in the genome which enable both the PcG and TrxG to bind which are called Polycomb/Trithorax response elements (PRE/TREs). These elements are well characterized in flies, but identifying and understanding mammalian PRE/TREs is one of the most controversial areas in the PcG/TrxG field.
We plan to explore the role of DNA sequence in epigenetic regulation in a systematic genome-wide computational approach in mammalian cells, followed by experimental testing of specific hypotheses.
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Publications
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Taei A., Rasooli P., Braun T., Hassani SN., Baharvand H. (2020). Signal regulators of human naïve pluripotency. Experimental Cell Research. 389(2):111924. (Abstract)
Suri F., Yazdani S., Chapi M., Safari I., Rasooli P., Daftarian N., Jafarinasab MR., Ghasemi Firouzabadi S., Alehabib E., Darvish H., Klotzle B., Fan JB., Turk C., Elahi E. (2018). COL18A1 is a candidate eye iridocorneal angle-closure gene in humans. Human Molecular Genetics. 27(21):3772-3786. (Article)
Jaberi E., Rohani M., Shahidi GA., Nafissi S., Arefian E., Soleimani M., Rasooli P., Ahmadieh H., Daftarian N., KaramiNejadRanjbar M., Klotzle B., Fan JB., Turk C., Steemers F., Elahi E. (2015). Identification of mutation in GTPBP2 in patients of a family with neurodegeneration accompanied by iron deposition in the brain. Neurobiology of Aging. 38: 216.e11-216.e18. (PubMed abstract)
InanlooRahatloo K., Zand Parsa AF., Huse K., Rasooli P., Davaran S., Gunderson K., Ronaghi M., Elahi E. (2014) Mutation in ST6GALNAC5 identified in family with coronary artery disease. Scientific Reports. 4:3595. (Article)
InanlooRahatloo K., Zand Parsa AF., Huse K., Rasooli P., Elahi E. (2013). Mutation in CYP27A1 identified in family with coronary artery disease. European Journal of Medical Genetics. 56(12):655:660. (Abstract)
Paylakhi SH., Moazzeni H., Yazdani S., Rassouli P., Arefian E., Jaberi E., Arash EH., Gilani AS., Fan JB., April C., Amin S., Suri F., Elahi E (2013). FOXC1 in human trabecular meshwork cells is involved in regulatory pathway that includes miR-204, MEIS2, and ITGb1. Experimental Eye Research. 111:112-121. (PubMed abstract)