Jordan Rowley, PhD

Assistant Professor 

   

Department of Genetics, Cell Biology and Anatomy
985805 Nebraska Medical Center
Omaha, NE 68198-5805

402-836-9794
Email

Education:
BS, Brigham Young University, Provo, UT, 2002 - 2008
PhD, University of Michigan, Ann Arbor, MI, 2009 - 2014
Emory University, Atlanta, GA, 2015 - 2019

Honors and Awards:
 K99/R00 Pathway to Independence Award, NIGMS, 2018 - 2022

Research:
Principles of 3D Chromatin Organization
Chromatin is deliberately arranged in the 3D nucleus so that genomic loci can influence each other long-range. The organization of chromatin is altered during development, in response to hormonal signaling, and after heat shock, indicating that the nucleus is a dynamic environment. Abnormal 3D chromatin organization is implicated in diseases such as aberrant limb formation, cancer, and embryonic lethality. My overall goal is to discover mechanisms driving the establishment and dynamics of 3D chromatin organization. Specifically, I aim to elucidate how looping, insulation, and transvection occur.

1. How are chromatin loops formed?
CTCF loops are a prominent feature of mammalian chromatin organization and are thought to alter enhancer – promoter interactions. The current model is that loops are formed via cohesion-mediated extrusion that is blocked by CTCF. How mammalian CTCF is able to block extrusion is unknown. Interestingly, Hi-C maps in Drosophila melanogaster do not display CTCF loops despite nearly identical DNA binding of the CTCF protein. Understanding why these differences occur will be a major focus of the lab.
   

2. How do architectural proteins contribute to pairing and transvection?
Transvection occurs via pairing of homologous chromosomes enabling enhancers on one chromosome to affect the expression of genes on the homologue. In Drosophila, homologous pairing of chromosomes occurs throughout interphase and is an important part of nuclear organization. Transvection is broadly affected by the presence or absence of architectural proteins, although it is unknown how. Pairing has been typically examined using low resolution FISH, but during my post-doctoral work I developed a method to examine homologous pairing at high resolution (~250 bp) using Hi-C data. I found that pairing occurs in “buttons” only a few kb in size, called hd-pairing sites. While condensin II was known to broadly inhibit pairing, I discovered that condensin II binds to hd-pairing sites partially unpairing them. By genome-wide analysis of hd-pairing sites, I also found that clustering of architectural proteins correlates with homologue pairing. My lab is interested in how these proteins affect pairing and/or transvection.

  
   

3. Predicting 3D chromatin organization
As we gain an understanding of 3D chromatin organization, my lab will use that data to improve algorithms to predict Hi-C maps from other data types. This will be useful to form new hypotheses on regions that fail prediction in wild-type cells, but also could be used to predict changes in the 3D chromatin landscape in response to various treatments.

  

Publications listed in PubMed

Publications:
  1. Fernandez-Albert J, Lipinski M, Lopez-Cascales MT, Rowley MJ, Martin-Gonzalez AM, Del Blanco B, Corces VG, Barco A. Immediate and deferred epigenomic signatures of in vivo neuronal activation in mouse hippocampus. Nat Neurosci. 2019 Oct;22(10):1718-1730. doi: 10.1038/s41593-019-0476-2. Epub 2019 Sep 9. PubMed PMID: 31501571.
  2. Gutierrez-Perez I, Rowley MJ, Lyu X, Valadez-Graham V, Vallejo DM, Ballesta-Illan E, Lopez-Atalaya JP, Kremsky I, Caparros E, Corces VG, Dominguez M. Ecdysone-Induced 3D Chromatin Reorganization Involves Active Enhancers Bound by Pipsqueak and Polycomb. Cell Rep. 2019 Sep 3;28(10):2715-2727.e5. doi: 10.1016/j.celrep.2019.07.096. PubMed PMID: 31484080; PubMed Central PMCID: PMC6754745.
  3. Jung YH, Kremsky I, Gold HB, Rowley MJ, Punyawai K, Buonanotte A, Lyu X, Bixler BJ, Chan AWS, Corces VG. Maintenance of CTCF- and Transcription Factor-Mediated Interactions from the Gametes to the Early Mouse Embryo. Mol Cell. 2019 Jul 11;75(1):154-171.e5. doi: 10.1016/j.molcel.2019.04.014. Epub 2019 May 2. PubMed PMID: 31056445; PubMed Central PMCID: PMC6625867.
  4. Rowley MJ, Lyu X, Rana V, Ando-Kuri M, Karns R, Bosco G, Corces VG. Condensin II Counteracts Cohesin and RNA Polymerase II in the Establishment of 3D Chromatin Organization. Cell Rep. 2019 Mar 12;26(11):2890-2903.e3. doi: 10.1016/j.celrep.2019.01.116. PubMed PMID: 30865881; PubMed Central PMCID: PMC6424357.
  5. Rowley MJ, Corces VG. Organizational principles of 3D genome architecture. Nat Rev Genet. 2018 Dec;19(12):789-800. doi: 10.1038/s41576-018-0060-8. Review. PubMed PMID: 30367165; PubMed Central PMCID: PMC6312108.
  6. Lyu X, Rowley MJ, Corces VG. Architectural Proteins and Pluripotency Factors Cooperate to Orchestrate the Transcriptional Response of hESCs to Temperature Stress. Mol Cell. 2018 Sep 20;71(6):940-955.e7. doi: 10.1016/j.molcel.2018.07.012. Epub 2018 Aug 16. PubMed PMID: 30122536; PubMed Central PMCID: PMC6214669.
  7. Ando-Kuri M, Rivera ISM, Rowley MJ, Corces VG. Analysis of Chromatin Interactions Mediated by Specific Architectural Proteins in Drosophila Cells. Methods Mol Biol. 2018;1766:239-256. doi: 10.1007/978-1-4939-7768-0_14. PubMed PMID: 29605857; PubMed Central PMCID: PMC6334841.
  8. Rowley MJ, Nichols MH, Lyu X, Ando-Kuri M, Rivera ISM, Hermetz K, Wang P, Ruan Y, Corces VG. Evolutionarily Conserved Principles Predict 3D Chromatin Organization. Mol Cell. 2017 Sep 7;67(5):837-852.e7. doi: 10.1016/j.molcel.2017.07.022. Epub 2017 Aug 17. PubMed PMID: 28826674; PubMed Central PMCID: PMC5591081.
  9. Rowley MJ, Rothi MH, Böhmdorfer G, Kuciński J, Wierzbicki AT. Long-range control of gene expression via RNA-directed DNA methylation. PLoS Genet. 2017 May;13(5):e1006749. doi: 10.1371/journal.pgen.1006749. eCollection 2017 May. PubMed PMID: 28475589; PubMed Central PMCID: PMC5438180.
  10. Cubeñas-Potts C, Rowley MJ, Lyu X, Li G, Lei EP, Corces VG. Different enhancer classes in Drosophila bind distinct architectural proteins and mediate unique chromatin interactions and 3D architecture. Nucleic Acids Res. 2017 Feb 28;45(4):1714-1730. doi: 10.1093/nar/gkw1114. PubMed PMID: 27899590; PubMed Central PMCID: PMC5389536.
  11. Gómez-Díaz E, Yerbanga RS, Lefèvre T, Cohuet A, Rowley MJ, Ouedraogo JB, Corces VG. Epigenetic regulation of Plasmodium falciparum clonally variant gene expression during development in Anopheles gambiae. Sci Rep. 2017 Jan 16;7:40655. doi: 10.1038/srep40655. PubMed PMID: 28091569; PubMed Central PMCID: PMC5238449.
  12. Rowley MJ, Corces VG. Capturing native interactions: intrinsic methods to study chromatin conformation. Mol Syst Biol. 2016 Dec 9;12(12):897. doi: 10.15252/msb.20167438. PubMed PMID: 27940491; PubMed Central PMCID: PMC5199123.
  13. Böhmdorfer G, Sethuraman S, Rowley MJ, Krzyszton M, Rothi MH, Bouzit L, Wierzbicki AT. Long non-coding RNA produced by RNA polymerase V determines boundaries of heterochromatin. 2016 Oct 25;5. doi: 10.7554/eLife.19092. PubMed PMID: 27779094; PubMed Central PMCID: PMC5079748.
  14. Rowley MJ, Corces VG. Minute-Made Data Analysis: Tools for Rapid Interrogation of Hi-C Contacts. Mol Cell. 2016 Oct 6;64(1):9-11. doi: 10.1016/j.molcel.2016.09.029. PubMed PMID: 27716489; PubMed Central PMCID: PMC5289287.
  15. Rowley MJ, Corces VG. The three-dimensional genome: principles and roles of long-distance interactions. Curr Opin Cell Biol. 2016 Jun;40:8-14. doi: 10.1016/j.ceb.2016.01.009. Epub 2016 Feb 4. Review. PubMed PMID: 26852111; PubMed Central PMCID: PMC4887315.
  16. Ye R, Chen Z, Lian B, Rowley MJ, Xia N, Chai J, Li Y, He XJ, Wierzbicki AT, Qi Y. A Dicer-Independent Route for Biogenesis of siRNAs that Direct DNA Methylation in Arabidopsis. Mol Cell. 2016 Jan 21;61(2):222-35. doi: 10.1016/j.molcel.2015.11.015. Epub 2015 Dec 17. PubMed PMID: 26711010; PubMed Central PMCID: PMC5110219.
  17. Böhmdorfer G, Rowley MJ, Kuciński J, Zhu Y, Amies I, Wierzbicki AT. RNA-directed DNA methylation requires stepwise binding of silencing factors to long non-coding RNA. Plant J. 2014 Jul;79(2):181-91. doi: 10.1111/tpj.12563. Epub 2014 Jun 23. PubMed PMID: 24862207; PubMed Central PMCID: PMC4321213.
  18. Rowley MJ, Böhmdorfer G, Wierzbicki AT. Analysis of long non-coding RNAs produced by a specialized RNA polymerase in Arabidopsis thaliana. 2013 Sep 15;63(2):160-9. doi: 10.1016/j.ymeth.2013.05.006. Epub 2013 May 22. PubMed PMID: 23707621; PubMed Central PMCID: PMC5107611.
  19. Zhu Y, Rowley MJ, Böhmdorfer G, Wierzbicki AT. A SWI/SNF chromatin-remodeling complex acts in noncoding RNA-mediated transcriptional silencing. Mol Cell. 2013 Jan 24;49(2):298-309. doi: 10.1016/j.molcel.2012.11.011. Epub 2012 Dec 13. PubMed PMID: 23246435; PubMed Central PMCID: PMC3560041.
  20. Zheng Q, Rowley MJ, Böhmdorfer G, Sandhu D, Gregory BD, Wierzbicki AT. RNA polymerase V targets transcriptional silencing components to promoters of protein-coding genes. Plant J. 2013 Jan;73(2):179-89. doi: 10.1111/tpj.12034. Epub 2012 Nov 9. PubMed PMID: 23013441; PubMed Central PMCID: PMC5096367.
  21. Wierzbicki AT, Cocklin R, Mayampurath A, Lister R, Rowley MJ, Gregory BD, Ecker JR, Tang H, Pikaard CS. Spatial and functional relationships among Pol V-associated loci, Pol IV-dependent siRNAs, and cytosine methylation in the Arabidopsis epigenome. Genes Dev. 2012 Aug 15;26(16):1825-36. doi: 10.1101/gad.197772.112. Epub 2012 Aug 1. PubMed PMID: 22855789; PubMed Central PMCID: PMC3426761.
  22. Rowley MJ, Avrutsky MI, Sifuentes CJ, Pereira L, Wierzbicki AT. Independent chromatin binding of ARGONAUTE4 and SPT5L/KTF1 mediates transcriptional gene silencing. PLoS Genet. 2011 Jun;7(6):e1002120. doi: 10.1371/journal.pgen.1002120. Epub 2011 Jun 9. PubMed PMID: 21738482; PubMed Central PMCID: PMC3111484.