# Investigation of the role of TET proteins in epigenetic reprogramming and establishment of germline imprinting > **NIH NIH F32** · UNIVERSITY OF PENNSYLVANIA · 2020 · $65,310 ## Abstract Project abstract: Genomic imprinting is a form of epigenetic regulation that restricts expression of a critical subset of genes to one parental allele. Imprinted gene expression is primarily regulated by differential methylation, which is acquired during gametogenesis, between the two parental alleles on cis-acting elements known as imprinting control regions (ICRs). Asymmetric patterns of active or repressive histone tail post-translational modifications (PTMs) further reinforce the monoallelic expression of imprinted loci. In humans, abnormal expression of imprinted genes is associated with imprinting disorders such as Beckwith-Wiedemann and Prader-Willi syndromes. Methylation at ICRs is stable throughout development and is only dynamically modulated during primordial germ cell (PGC) development and gametogenesis. In mammals, PGCs are derived from the somatic epiblast and undergo epigenome reprogramming in order to: 1) prevent the transmission of gestationally acquired epimutations to the next generation and 2) erase the parentally-inherited somatic imprinting marks to allow for the acquisition of new imprints that are consistent with the sex of the embryo. Previous work from our laboratory and others have implicated the role of TET1, a methylcytosine dioxygenase, in the establishment of proper imprinting marks in the mature male and female gametes. My preliminary data suggest that while TET1 is necessary for complete methylation erasure of a subset of ICRs in PGCs, it also plays a previously unexplored role of protecting paternally methylated ICRs from gaining ectopic methylation in the oocytes. As TET1 is a large protein with the ability to interact with and influence activities of various chromatin remodelers, I hypothesize a novel non-catalytic role for TET1 in promoting the proper establishment of germline imprints by remodeling the broader chromatin landscape of ICRs. The objective of this proposal is to investigate how the remodeled chromatin landscape of ICRs in PGC development contributes to the proper acquisition of sex- specific DNA methylation patterns during oogenesis. In Aim 1, I will test the hypothesis that TET1 facilitates chromatin remodeling of the ICRs during methylation erasure in PGCs. I will use allele-specific cleavage under targets and release using nuclease (CUT&RUN) to assess the efficiency of chromatin reprogramming in Tet1-/- hybrid PGCs. In Aim 2, I will identify loci, in addition to paternally methylated ICRs, which ectopically gain methylation during oogenesis in absence of TET1. To investigate the mechanism underlying ectopic de novo methylation in Tet1-/- oocytes, I will investigate the status of histone PTMs that are associated with DNA methyltransferase-resistant chromatin landscape at paternally methylated ICRs in Tet1-/- oocytes using CUT&RUN. Collectively, this proposal will elucidate the catalytic and non-catalytic functions of TET1 in the establishment of the proper chromatin landscape at ICRs and the co... ## Key facts - **NIH application ID:** 10066993 - **Project number:** 1F32HD101230-01A1 - **Recipient organization:** UNIVERSITY OF PENNSYLVANIA - **Principal Investigator:** Rexxi Diptya Prasasya - **Activity code:** F32 (R01, R21, SBIR, etc.) - **Funding institute:** NIH - **Fiscal year:** 2020 - **Award amount:** $65,310 - **Award type:** 1 - **Project period:** 2020-09-01 → 2023-08-31 ## Primary source NIH RePORTER: https://reporter.nih.gov/project-details/10066993 ## Citation > US National Institutes of Health, RePORTER application 10066993, Investigation of the role of TET proteins in epigenetic reprogramming and establishment of germline imprinting (1F32HD101230-01A1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10066993. Licensed CC0. --- *[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*