Identification and characterization of new epigenetic modifications
We seek to identify new epigenetic and epitranscriptomic modifications, the enzymes which regulate these modifications, and their role in a variety of biological processes. Current projects are focused on how epigenetic modifications can regulate cancer metastasis, longevity, and stress resistance in a variety of model organisms. For example, we have identified PCIF1 as an mRNA methyltransferase which adds a methyl group to adenosines on the cap of mRNAs in mice and humans to produce a dually methylated adenosine (m6Am).
Our current projects examine the biological function of this capping mechanism in processes such as viral replication and neural development. We also identified the enzyme METL-5 as a m6A methyltransferase which methylates a single residue on the 18S ribosomal rRNA to regulate lipid oxidation and stress resistance in C. elegans. Our identification of METL-5 as an 18S rRNA methyltransferase has taken us into the field of ribosome heterogeneity and lipid signaling.
Publications
DNA Methylation on N6-Adenine in C. elegans
February 1, 2016
Greer EL, Blanco MA, Gu L, Sendinc E, Liu J, Aristizábal-Corrales D, Hsu CH, Aravind L, He C, Shi Y. DNA Methylation on N6-Adenine in C. elegans. Cell. 2015 May 7;161(4):868-78. doi: 10.1016/j.cell.2015.04.005. Epub 2015 Apr 30. PMID: 25936839; PMCID: PMC4427530.
Sources of artifact in measurements of 6mA and 4mC abundance in eukaryotic genomic DNA
June 3, 2019
O’Brown ZK, Boulias K, Wang J, Wang SY, O’Brown NM, Hao Z, Shibuya H, Fady PE, Shi Y, He C, Megason SG, Liu T, Greer EL. Sources of artifact in measurements of 6mA and 4mC abundance in eukaryotic genomic DNA. BMC Genomics. 2019 Jun 3;20(1):445. doi: 10.1186/s12864-019-5754-6. PMID: 31159718; PMCID: PMC6547475.
Identification of the m6Am Methyltransferase PCIF1 Reveals the Location and Functions of m6Am in the Transcriptome
August 8, 2019
Boulias K, Toczydłowska-Socha D, Hawley BR, Liberman N, Takashima K, Zaccara S, Guez T, Vasseur JJ, Debart F, Aravind L, Jaffrey SR, Greer EL. Identification of the m6Am Methyltransferase PCIF1 Reveals the Location and Functions of m6Am in the Transcriptome. Mol Cell. 2019 Aug 8;75(3):631-643.e8. doi: 10.1016/j.molcel.2019.06.006. Epub 2019 Jul 3. PMID: 31279658; PMCID: PMC6703822.
The demethylase NMAD-1 regulates DNA replication and repair in the Caenorhabditis elegans germline
July 8, 2019
Wang SY, Mao H, Shibuya H, Uzawa S, O’Brown ZK, Wesenberg S, Shin N, Saito TT, Gao J, Meyer BJ, Colaiácovo MP, Greer EL. The demethylase NMAD-1 regulates DNA replication and repair in the Caenorhabditis elegans germline. PLoS Genet. 2019 Jul 8;15(7):e1008252. doi: 10.1371/journal.pgen.1008252. PMID: 31283754; PMCID: PMC6638966.
N6-adenosine methylation of ribosomal RNA affects lipid oxidation and stress resistance
April 22, 2020
Liberman N, O’Brown ZK, Earl AS, Boulias K, Gerashchenko MV, Wang SY, Fritsche C, Fady PE, Dong A, Gladyshev VN, Greer EL. N6-adenosine methylation of ribosomal RNA affects lipid oxidation and stress resistance. Sci Adv. 2020 Apr 22;6(17):eaaz4370. doi: 10.1126/sciadv.aaz4370. PMID: 32494643; PMCID: PMC7176415.
Detection of DNA Methylation in Genomic DNA by UHPLC-MS/MS
August 22, 2020
Boulias K, Greer EL. Detection of DNA Methylation in Genomic DNA by UHPLC-MS/MS. Methods Mol Biol. 2021;2198:79-90. doi: 10.1007/978-1-0716-0876-0_7. PMID: 32822024; PMCID: PMC8281577.
Methylation of viral mRNA cap structures by PCIF1 attenuates the antiviral activity of interferon-β
July 20, 2021
Tartell MA, Boulias K, Hoffmann GB, Bloyet LM, Greer EL, Whelan SPJ. Methylation of viral mRNA cap structures by PCIF1 attenuates the antiviral activity of interferon-β. Proc Natl Acad Sci U S A. 2021 Jul 20;118(29):e2025769118. doi: 10.1073/pnas.2025769118. PMID: 34266951; PMCID: PMC8307471.