Jesse Mager

Jesse Mager, Ph.D.

Associate Professor



Jesse Mager, Ph.D.

Office phone: 413-545-7368

Lab phone: 413-545-2339

Fax: 413-545-6326

Email: jmager [at] vasci [dot] umass [dot] edu

Office location: 427M ISB

Ph.D.: University of North Carolina
Postdoc Training: University of Pennsylvania

ANIML SCI 311 - Animal Genetics
ANIML SCI 697J - Cells, Genes and Development
ANIML SCI 795A - Journal Club: Cells, Genes & Development

Developmental Epigenetics

Comrehensive genome sequencing has the potential to dramatically improve our understanding of the genetic underpinnings of normal biology and disease states. Uncovering how complex genomes are epigenetically modified and identification of the protein and RNA mediators responsible is a critical next step towards understanding the dynamic changes that occur throughout development and differentiation. My interests lie in understanding this epigenetic regulation of mammalian genomes, and we use the earliest stages of mouse development as a model system. Although brief in time, preimplantation development is an extremely dynamic period during which major epigenetic remodeling occurs, and the very first cell fate decisions are made. These key biological processes require global, yet exquisitely precise chromatin remodeling. We utilize various RNAi approaches towards identification of genes that regulate these earliest epigenetic decisions that occur during oogenesis and preimplantation development.

Preimplantation RNAi and epigenetic reporters

Epigenetic regulation during preimplantation development begins with the remodeling of egg and sperm haploid genomes prior to pronuclear fusion. By the time of blastocyst formation (3.5 days post fertilization in the mouse), differential chromatin structure has been established at sites throughout the genome, including parent of origin imprinted domains as well as trophoblast and ICM specific gene expression. To capitalize on the manipulability of this early window of epigenetic reorganization, we knock-down candidate transcripts by injecting or electroporating long dsRNAs into single cell embryos, followed by in-vitro culture until the blastocyst stage.

Genome imprinting is an epigenetic mechanism resulting in differential transcriptional activity between the two parental alleles. It is well established that differential chromatin structure accompanies this parent of origin gene expression. More specifically, DNA hypo/hyper-methylation, and core histone modifications (acetylation/methylation) differ between the active and silent alleles. Disruption of any one of these chromatin modifications may result in loss of imprinting at particular loci, making imprinted genes sensitive “reporters” of epigenetic regulatory mechanisms. In addition to harboring the necessary polymorphisms for imprinting and X inactivation assays, the mouse strains used for the phenotypic screen also carry an EGFP transgene driven by the Oct4 promoter, which is specifically expressed in the ICM at the blastocyst stage. We therefore screen for loss of imprinting, defects in trophoblast/ICM differentiation, as well as developmental arrest and morphological abnormalities all within the same embryos. To date we have funtionally assessed more than 600 genes with this strategy and identified many novel phenoytpes.

Preimplantation RNAi screen overflow

Regulation of Genomic Imprinting During Gastrulation

Genomic imprinting is an epigenetic phenomenon that results in parent of origin mono-allelic gene expression. The majority of imprinted genes reside in coordinately regulated clusters containing oppositely imprinted transcripts. Although allele specific DNA methylation and histone modifications have been shown at many imprinted loci, tissue and temporal specific mechanisms in vivo that establish and interpret these epigenetic marks are not fully defined. The mechanisms that regulate establishment and interpretation of epigenetic marks at imprinted loci are also essential for reprogramming – both during development in vivo and during induced pluripotency and somatic cell cloning.   Thus, understanding the full cadre of in vivo mechanisms regulating epigenetic events will guide our derivation and use of pluripotent cells.

We have discovered tissue specific regulation of genomic imprinting at the Igf2r locus during gastrulation in vivo. At the Igf2r/Airn imprinted cluster, paternal expression of the long non-coding RNA Airn has been shown to silence the paternal alleles of Igf2r, Slc22a2, and Slc22a3 resulting in maternal expression of these genes, and reciprocal imprinting at the locus. We have found that imprinting of Igf2r and Airn is regulated differently in distinct gastrulation lineages. Although imprinted expression is present in extraembryonic tissues at all stages, Igf2r is biallelic and Airn is not expressed in the epiblast prior to gastrulation. Once gastrulation commences, Igf2r and Airn become reciprocally imprinted. We also observe spreading of DNA methylation coincident with the start of gastrulation. Importantly, these results indicate epigenetic alterations occur as the epiblast differentiates into embryonic lineages, similar to what occurs as the zygotic genome is reprogrammed during preimplantation development.  We are continuing to define the mechanisms that are necessary and sufficient to achieve distinct lineage specific regulation of imprinting during gastrulation and determine the extent of epigenetic alterations in the newly formed germ layers using next-generation sequencing techniques.


Daneshvar K, Pondick JV, Kim BM, Zhou C, York SR, Macklin JA, Abualteen A, Tan B, Sigova AA, Marcho C, Tremblay KD, Mager J, Choi MY, Mullen AC. Cell Rep. 2016 Oct 4;17(2):353-365. DIGIT Is a Conserved Long Noncoding RNA that Regulates GSC Expression to Control Definitive Endoderm Differentiation of Embryonic Stem Cells. doi:10.1016/j.celrep.2016.09.017. PMID: 27705785

Cui W, Dai X, Marcho C, Han Z, Zhang K, Tremblay KD, Mager J.;Sci Rep. 2016 Nov 21;6:37396. Towards Functional Annotation of the Preimplantation Transcriptome: An RNAi Screen in Mammalian Embryos. doi: 10.1038/srep37396. PMID: 27869233

Navarrete FA, Alvau A, Lee HC, Levin LR, Buck J, Leon PM, Santi CM, Krapf D, Mager J, Fissore RA, Salicioni AM, Darszon A, Visconti PE.; Sci Rep. 2016 Sep 15;6:33589. Transient exposure to calcium ionophore enables in vitro fertilization in sterile mouse models.doi:10.1038/srep33589.
PMID: 27627854

Wallingford MC, Hiller J, Zhang K, Mager J.  2017.  YY1 Is Required for Posttranscriptional Stability of SOX2 and OCT4Proteins. Cellular Reprogramming. 19:263–269.
Cui W, Mager J.  2017.  Transcriptional Regulation and Genes Involved in First Lineage Specification During Preimplantation Development. Chromatin Regulation of Early Embryonic Lineage Specification. :31–46.
Cui W, Dai X, Marcho C, Han Z, Zhang K, Tremblay KD, Mager J.  2016.  Towards Functional Annotation of the Preimplantation Transcriptome: An RNAi Screen in Mammalian Embryos. Scientific Reports. 6
Prasad P, Molla MR, Cui W, Canakci M, Osborne B, Mager J, Thayumanavan S.  2015.  Polyamide Nanogels from Generally Recognized as Safe Components and Their Toxicity in Mouse Preimplantation Embryos.. Biomacromolecules. 16(11):3491-8.
Beketaev I, Zhang Y, Weng K-C, Rhee S, Yu W, Liu Y, Mager J, Wang J.  2015.  cis-regulatory control of Mesp1 expression by YY1 and SP1 during mouse embryogenesis. Developmental Dynamics. 245:379–387.
Marcho C, Cui W, Mager J.  2015.  Epigenetic dynamics during preimplantation development. Reproduction. 150:R109–R120.
Marcho C, Bevilacqua A, Tremblay KD, Mager J.  2015.  Tissue-specific regulation of Igf2r/Airn imprinting during gastrulation.. Epigenetics Chromatin. 8:10.
Washkowitz AJ, Schall C, Zhang K, Wurst W, Floss T, Mager J, Papaioannou VE.  2015.  Mga is essential for the survival of pluripotent cells during peri-implantation development.. Development. 142(1):31-40.
Cui W, Pizzollo J, Han Z, Marcho C, Zhang K, Mager J.  2015.  Nop2 is required for mammalian preimplantation development.. Mol Reprod Dev.
Beketaev I, Zhang Y, Weng K-C, Rhee S, Yu W, Liu Y, Mager J, Wang J.  2015.  cis-regulatory control of Mesp1 expression by YY1 and SP1 during mouse embryogenesis.. Dev Dyn.
Shin JD, Wallingford MC, Gallant J, Marcho C, Jiao B, Byron M, Bossenz M, Lawrence JB, Jones SN, Mager J et al..  2014.  RLIM is dispensable for X-chromosome inactivation in the mouse embryonic epiblast.. Nature. 511(7507):86-9.
Wallingford MC, Filkins R, Adams D, Walentuk M, Salicioni AM, Visconti PE, Mager J.  2014.  Identification of a novel isoform of the leukemia-associated MLLT1 (ENL/LTG19) protein.. Gene Expr Patterns. 17(1):11-15.
Wertheimer E, Krapf D, Vega-Beltran JL, Sánchez-Cárdenas C, Navarrete F, Haddad D, Escoffier J, Salicioni AM, Levin LR, Buck J et al..  2013.  Compartmentalization of Distinct cAMP Signaling Pathways in Mammalian Sperm.. J Biol Chem.
Wallingford MC, Angelo JR, Mager J.  2013.  Morphogenetic analysis of peri-implantation development.. Dev Dyn. 242(9):1110-20.
Rhee S, Guerrero-Zayas M-I, Wallingford MC, Ortiz-Pineda P, Mager J, Tremblay KD.  2013.  Visceral endoderm expression of Yin-Yang1 (YY1) is required for VEGFA maintenance and yolk sac development.. PLoS One. 8(3):e58828.
Maserati M, Dai X, Walentuk M, Mager J.  2012.  Identification of 4 genes required for mammalian blastocyst formation.. Zygote. In Press
Zhang K, Dai X, Wallingford MC, Mager J.  2012.  Depletion of Suds3 reveals an essential role in early lineage specification.. Developmental biology.
Maserati M, Walentuk M, Dai X, Holston O, Adams D, Mager J.  2011.  Wdr74 is required for blastocyst formation in the mouse.. PloS one. 6(7):e22516.
Trask MC, Mager J.  2011.  Complexity of polycomb group function: diverse mechanisms of target specificity.. Journal of cellular physiology. 226(7):1719-21.
Griffith GJ, Trask MC, Hiller J, Walentuk M, Pawlak JB, Tremblay KD, Mager J.  2011.  Yin-yang1 is required in the mammalian oocyte for follicle expansion.. Biology of reproduction. 84(4):654-63.
Weaver JR, Sarkisian G, Krapp C, Mager J, Mann MRW, Bartolomei MS.  2010.  Domain-specific response of imprinted genes to reduced DNMT1.. Molecular and cellular biology. 30(16):3916-28.
Malcuit C, Trask MC, Santiago L, Beaudoin E, Tremblay KD, Mager J.  2009.  Identification of novel oocyte and granulosa cell markers.. Gene expression patterns : GEP. 9(6):404-10.
Yoon S-Y, Jellerette T, Salicioni AM, Lee HC, Yoo M-S, Coward K, Parrington J, Grow D, Cibelli JB, Visconti PE et al..  2008.  Human sperm devoid of PLC, zeta 1 fail to induce Ca(2+) release and are unable to initiate the first step of embryo development.. The Journal of clinical investigation. 118(11):3671-81.
Rivera RM, Stein P, Weaver JR, Mager J, Schultz RM, Bartolomei MS.  2008.  Manipulations of mouse embryos prior to implantation result in aberrant expression of imprinted genes on day 9.5 of development.. Human molecular genetics. 17(1):1-14.
Mager J, Schultz RM, Brunk BP, Bartolomei MS.  2006.  Identification of candidate maternal-effect genes through comparison of multiple microarray data sets.. Mammalian genome : official journal of the International Mammalian Genome Society. 17(9):941-9.
Mager J, Bartolomei MS.  2005.  Strategies for dissecting epigenetic mechanisms in the mouse.. Nature genetics. 37(11):1194-200.
Rivera-Pérez JA, Mager J, Magnuson T.  2003.  Dynamic morphogenetic events characterize the mouse visceral endoderm.. Developmental biology. 261(2):470-87.
Wang J, Mager J, Chen Y, Schneider E, Cross JC, Nagy A, Magnuson T.  2001.  Imprinted X inactivation maintained by a mouse Polycomb group gene.. Nature genetics. 28(4):371-5.
Name Phone Office
Degani , Rinat Research Technician 413-545-2339 ISB 455
Cheong , Agnes Ph.D. candidate 413-545-2339 ISB 455
Crowley , Stephanie Undergraduate Research Assistant 413-545-2339 ISB 455
Curley , Erin Undergraduate Research Assistant 413-545-2339 ISB 455
Deane , Amanda Undergraduate Research Assistant 413-545-2339 ISB 455
Hill , Dalton Undergraduate Research Assistant 413-545-2339 ISB 455
Marcho , Chelsea MCB Graduate Student 413-545-7372 ISB 455
Moon , Yoonjin Undergraduate Research Assistant 413-545-2339 ISB 455
Tellier , Adam Undergraduate Research Assistant 413-545-2339 ISB 455
Volvovitz , Ben Undergraduate Research Assistant 413-545-2339 ISB 455