The research in my laboratory focuses on the study of genomic imprinting and X inactivation in mice.
genomic imprinting, X inactivation, DNA methylation, epigenetics, environment.
Description of Research
One aspect of the research in my laboratory focuses on the study of genomic imprinting in mice. While affecting only a subset of genes in mammals, genomic imprinting results in the unequal expression of the maternal and paternal alleles of a gene. As a consequence, the maternal and paternal genomes are functionally non-equivalent and both are required for normal mammalian development. One imprinted gene, H19, is exclusively expressed from the maternally-derived allele in mice and humans. There are a number of important questions concerning the control of imprinting that are being addressed using the mouse H19 gene. These questions include how and when the inactive and active alleles are differentiated, what sequences designate that a gene is to be imprinted, and what factors function to imprint the gene. Moreover, we are also determining how the environment, including procedures used in Assisted Reproductive Technologies (ART) and endocrine disruptors, affect imprinting and epigenetic gene regulation.
My laboratory also studies the process of X inactivation in mice. X inactivation is the dosage compensation mechanism that female mammals use to silence one X chromosome and to achieve equivalent X-linked expression to males. Certain aspects of this complex multi-step process have been well established, but the molecular and genetic mechanisms controlling this process remain poorly characterized. To isolate factors involved in X inactivation we have employed the following strategies: we have collaborated with Huntington Willard (Duke University) in conducting ENU mutagenesis in the mouse to select for mutations that affect X inactivation; we have participated in studies that assay reactivation of X-linked genes; and we have examined the effects of various mutations and environmental perturbations on X inactivation.
1. Analysis (expression, DNA methylation and higher order chromatin structure) of mice harboring mutations at imprinted loci.
2. Examination of the effects of various environmental perturbations on imprinting status, including environmental estrogens and procedures used in Assisted Reproductive Technologies.
3. Examination of noncoding RNAs at the H19/Igf2 locus.
4. Analysis of DNA methylation reprogramming in the germline.
5. Other projects available by speaking with PI.
Graduate Students: Aimee Juan, Nicole Robles-Matos, YeeHoon Foong, Zhengfeng (Jeff) Liu, Cassidy Hemphill
Research Associate: Joanne Thorvaldsen
Postdoctoral Fellow: : Eric Rhon-Calderon, Rexxi Prasasya, Yahan Li
Research Technicians: Christopher Krapp
Undergraduates: Kashish Wadhwa, Alexis Kaiser, Songze Wu
Juan, A.M., Foong, Y.H., Thorvaldsen, J.L., Lan, Y., Leu, N.A., Rurik, J.G., Krapp, C., Rosier, C.L., Epstein, J.A. and M.S. Bartolomei.: Tissue-specific Grb10/Ddc insulator drives allelic archietecture for cardiac development. Molecular Cell 82: 3613, October 2022.
Caldwell, B.A., Liu, M.Y., Prasasya, R.D., Wang, T., DeNizio, J.E., Leu, N.A., Amoh, N.Y.A., Krapp, C., Lan, Y., Shields, E.J., Bonasio, R., Lengner, C.J., Kohli, R.M. and M.S. Bartolomei : Functionally distinct roles for TET-oxidized 5-methylcytosine bases in somatic reprogramming to pluripotency. Molecular Cell 81: 859-869, February 2021.
Vrooman, L.A., Rhon-Calderon, E.A., Chao, O.Y., Nguyen, D.K., Narapareddy, L, Dahiya, A.K., Putt, M.E., Schultz, R.M., and M.S. Bartolomei: Assisted reproductive technologies induce temporally-specific placental defects and risk for preeclampsia in a mouse model.
Development 147:dev186551, May 2020.
SanMiguel Jennifer M, Abramowitz Lara K, Bartolomei Marisa S: Imprinted gene dysregulation in a null mouse model is stochastic and variable in the germline and offspring. Development (Cambridge, England) 145(7), Mar 2018.
Wang Ting, Pehrsson Erica C, Purushotham Deepak, Li Daofeng, Zhuo Xiaoyu, Zhang Bo, Lawson Heather A, Province Michael A, Krapp Christopher, Lan Yemin, Coarfa Cristian, Katz Tiffany A, Tang Wan Yee, Wang Zhibin, Biswal Shyam, Rajagopalan Sanjay, Colacino Justin A, Tsai Zing Tsung-Yeh, Sartor Maureen A, Neier Kari, Dolinoy Dana C, Pinto Jayant, Hamanaka Robert B, Mutlu Gokhan M, Patisaul Heather B, Aylor David L, Crawford Gregory E, Wiltshire Tim, Chadwick Lisa H, Duncan Christopher G, Garton Amanda E, McAllister Kimberly A, Bartolomei Marisa S, Walker Cheryl L, Tyson Frederick L: The NIEHS TaRGET II Consortium and environmental epigenomics. Nature biotechnology 36(3): 225-227, Mar 2018.
Hur Stella K, Freschi Andrea, Ideraabdullah Folami, Thorvaldsen Joanne L, Luense Lacey J, Weller Angela H, Berger Shelley L, Cerrato Flavia, Riccio Andrea, Bartolomei Marisa S: Humanized H19/Igf2 locus reveals diverged imprinting mechanism between mouse and human and reflects Silver-Russell syndrome phenotypes. Proceedings of the National Academy of Sciences of the United States of America 113(39): 10938-43, Sep 2016.
Ginart Paul, Kalish Jennifer M, Jiang Connie L, Yu Alice C, Bartolomei Marisa S, Raj Arjun: Visualizing allele-specific expression in single cells reveals epigenetic mosaicism in an H19 loss-of-imprinting mutant. Genes & development 30(5): 567-78, Mar 2016.
Plasschaert Robert N, Bartolomei Marisa S: Tissue-specific regulation and function of Grb10 during growth and neuronal commitment. Proceedings of the National Academy of Sciences of the United States of America 112(22): 6841-7, Jun 2015.
de Waal Eric, Vrooman Lisa A, Fischer Erin, Ord Teri, Mainigi Monica A, Coutifaris Christos, Schultz Richard M, Bartolomei Marisa S: The cumulative effect of assisted reproduction procedures on placental development and epigenetic perturbations in a mouse model. Human molecular genetics 24(24): 6975-85, Dec 2015.
Venkatraman Aparna, He Xi C, Thorvaldsen Joanne L, Sugimura Ryohichi, Perry John M, Tao Fang, Zhao Meng, Christenson Matthew K, Sanchez Rebeca, Yu Jaclyn Y, Peng Lai, Haug Jeffrey S, Paulson Ariel, Li Hua, Zhong Xiao-Bo, Clemens Thomas L, Bartolomei Marisa S, Li Linheng: Maternal imprinting at the H19-Igf2 locus maintains adult haematopoietic stem cell quiescence. Nature Jul 2013.
Susiarjo Martha, Sasson Isaac, Mesaros Clementina, Bartolomei Marisa S: Bisphenol a exposure disrupts genomic imprinting in the mouse. PLoS genetics 9(4): e1003401, Apr 2013.
Susiarjo Martha, Xin Frances, Bansal Amita, Stefaniak Martha, Li Changhong, Simmons Rebecca A, Bartolomei Marisa S: Bisphenol a exposure disrupts metabolic health across multiple generations in the mouse. Endocrinology 156(6): 2049-58, Jun 2015.
Plasschaert Robert N, Vigneau Sébastien, Tempera Italo, Gupta Ravi, Maksimoska Jasna, Everett Logan, Davuluri Ramana, Mamorstein Ronen, Lieberman Paul M, Schultz David, Hannenhalli Sridhar, Bartolomei Marisa S: CTCF binding site sequence differences are associated with unique regulatory and functional trends during embryonic stem cell differentiation. Nucleic acids research 42(2): 774-89, Jan 2014.
back to top
Last updated: 11/23/2022
The Trustees of the University of Pennsylvania