Dartmouth Medical School (Hanover, New Hampshire)
Our laboratory is devoted to understanding nuclear architecture and chromatin organization within human cells, especially myeloid cells. For many years we have studied the human leukemic HL-60 cell line, because it can be readily differentiated in vitro into granulocyte or macrophage forms. We have employed monoclonal anti-nucleosome antibodies to identify a new nuclear domain ("epichromatin"), which is adjacent to the interphase nuclear envelope and at the outer surface of mitotic chromosomes. Epichromatin can also be visualized by antibodies that react with phosphatidylserine (PS), the principal anionic phospholipid of cell membranes. Our current structural hypothesis is that PS forms a noncovalent bridge connecting the nuclear envelope inner membrane with the surface of chromatin displaying histone cationic peptide arms. In collaboration with scientists from the German Cancer Research Center (Heidelberg), we have performed (ChIP-Seq) chromatin immunoprecipitation followed by DNA sequencing to characterize the DNA associated with the epichromatin. We find a significant enrichment of repetitive DNA (i.e., retrotransposon Alu) within the epichromatin region. Furthermore, epichromatin regions have been mapped to the human chromosomes, demonstrating that only a small percentage of nuclear DNA is affiliated with these regions.
A second direction of research in the laboratory involves the nucleosome, which we first described in 1974, present as a 10 nm chain of chromatin "beads". For many years, a 30 nm diameter fiber was thought to be the next level of nucleosome compaction, but its existence has proven to be controversial. Recent collaborative studies with scientists at EMBL (Heidelberg) have demonstrated the existence of parallel arrays of 10 nm chromatin fibers adjacent to the nuclear envelope in HL-60 granulocytes, an indication of the structure of epichromatin.
Bing-Rui Zhou, Sathish Yadav, Mario Borgnia, JingJun Hong, Baohua Cao, Donald E. Olins, Ada L. Olins, Yawen Bai , Ping Zhang. Atomic resolution cryo-EM structures of a native-like CENP-A nucleosomes aided by an antibody fragment (2019) (in press, Nature Communications)
Elsie Jacobson, Ralph S. Grand, Jo K. Perry, Mark H. Vickers, Ada L. Olins, Donald E. Olins, Justin M. O’Sullivan (2019), Hi-C detects novel structural variants in HL-60 and HL-60/S4 cell lines. (in press, Genomics)
Elsie C. Jacobson, Jo K. Perry, David S. Long, Ada L. Olins, Donald E. Olins, Bryon E. Wright, Mark H. Vickers, Justin M. O'Sullivan. (2018) Migration through a small pore disrupts inactive chromatin organisation in neutrophil-like cells. BMC Biology doi: 10.1186/s12915-018-0608-2
Giuseppe Chirico, Alexander Gansen, Sanford H. Leuba, Ada L. Olins, Donald E. Olins, Jeremy Smith, Katalin Toth (2018) Jörg Langowski: His Scientific Legacy and the Future It Promises. BMC Biophysics 11:5. doi: https://doi.org/10.1186/s13628-018-0045-1
Olins DE, Olins AL. (2018) Epichromatin and chromomeres: a ‘fuzzy’ perspective. Royal Society Open Biol. 8: 180058. http://dx.doi.org/10.1098/rsob.180058
Travis J. Gould, Katalin Tóth, Norbert Mücke, Jörg Langowski*, Alexandra S. Hakusui, Ada L. Olins, Donald E. Olins. (2017) Defining the Epichromatin Epitope. Nucleus 8(6) 625-640. doi.org/10.1080/19491034.2017.1380141.
Vladimir B Teif, Jan-Philipp Mallm, Tanvi Sharma, David B Mark Welch, Karsten Rippe, Roland Eils, Jörg Langowski, Ada L Olins, Donald E Olins. (2017) Nucleosome Repositioning During Differentiation of a Human Myeloid Leukemia Cell Line. Nucleus 8(2):188-204. doi: 10.1080/19491034.2017.1295201.
David B. Mark Welch, Anna Jauch, Jörg Langowski, Ada L. Olins and Donald E. Olins (2017). Transcriptomes reflect the Phenotypes of Undifferentiated, Granulocyte and Macrophage forms of HL-60/S4 cells. Nucleus 8(2):222-237. doi: 10.1080/19491034.2017.1285989
Ada L. Olins, Naveed Ishaque, Sasithorn Chotewutmontri, Jörg Langowski, Donald E. Olins (2014). Retrotransposon Alu is Enriched in the Epichromatin of HL-60 Cells. Nucleus 5:3 (237-246). doi:10.4161/nucl.29141
M . Derenzini, A.L. Olins, D.E. Olins. (2014) Chromatin structure in situ: the contribution of DNA ultrastructural cytochemistry. Eur J Histchem 58(1):2307-2316. doi: 10.4081/ejh.2014.2307.
Mikhail Eltsov, Sergey Sosnovski, Ada L. Olins, Donald E. Olins. (2014) ELCS in Ice: Cryo-electron Microscopy of Chromatin Sheets. Chromosoma 123:3 303-312. doi: 10.1007/s00412-014-0454-0.
Igor Prudovsky, Calvin P.H. Vary, Yolanda Markaki, Ada L. Olins and Donald E. Olins. (2012) Phosphatidylserine colocalizes with epichromatin in interphase nuclei and mitotic chromosomes. Nucleus 3:2, 200–210.
Ada L. Olins, Markus Langhans, Marc Monestier, Andreas Schlotterer, David G. Robinson, Corrado Viotti, Hanswalter Zentgraf, Monika Zwerger and Donald E. Olins. (2011) An epichromatin epitope: Persistence in the cell cycle and conservation in evolution Nucleus 2:1, 47-60.
Ada L. Olins, Aurélie Ernst, Monika Zwerger, Harald Herrmann and Donald E. Olins. (2010) An in vitro model for Pelger-Huët anomaly: Stable knockdown of lamin B receptor in HL-60 cells. Nucleus 1:6, 506-512.
Ada L. Olins, Gale Rhodes, David B. Mark Welch, Monika Zwerger and Donald E. Olins.(2010) Lamin B Receptor: Multi-tasking at the Nuclear Envelope. Nucleus 1:53-70.
Donald E. Olins and Ada L. Olins. (2009) Nuclear Envelope-Limited Chromatin Sheets (ELCS) and Heterochromatin Higher Order Structure. Chromosoma. 118:537-548.
Ada L. Olins, Thanh V. Hoang, Monika Zwerger, Harald Herrmann, Hanswalter Zentgraf, Angelika A. Noegel, Iakowos Karakesisoglou, Didier Hodzic and Donald E. Olins. (2009) The LINC-less granulocyte nucleus. Eur. J. Cell Biol. 88:203-214.
Peter Gaines, Chiung Wen Tien, Ada L. Olins, Donald E. Olins, Leonard D. Shultz, Lisa Carny and Nancy Berliner. (2008) Mouse neutrophils lacking lamin B receptor expression exhibit aberrant development and lack critical functional responses. Exp Hematol. 36(8):965-76.
Monika Zwerger, Harald Herrmann, Peter Gaines, Ada L. Olins, and Donald E.Olins. (2008) Granulocytic nuclear differentiation of lamin B receptor-deficient mouse EPRO cells. Exp Hematol. 36(8):977-87.
Ada L. Olins, Monika Zwerger, Harald Herrmann, Hanswalter Zentgraf, Amos J. Simon, Marc Monestier, Donald E. Olins. (2008) The Human Granulocyte Nucleus: Unusual Nuclear Envelope and Heterochromatin Composition. Eur J Cell Biol. 87(5):279-90.
Katrin Hoffmann, Karl Sperling, Ada L. Olins and Donald E. Olins. (2007) The granulocyte nucleus and lamin B receptor: avoiding the ovoid. Chromosoma 116:227-235.
Leonard D. Shultz, Bonnie L. Lyons, Lisa M. Burzenski, Bruce Gott , Rebecca Samuels, Peter A.Schweitzer, Christine Dreger, Harald Herrmann, Vera Kalscheuer, Ada L. Olins, Donald E. Olins, Karl Sperling and Katrin Hoffman. (2003) Mutations at the Murine Ichthyosis Locus are within the Lamin B Receptor Gene: A Single Gene Model for Human Pelger-Huët Anomaly. Hum Mol Genet 12: 61-69.
Hoffmann K, Dreger C, Olins AL, Olins DE, Shultz LD, Lucke B, Karl H, Kaps R, Mueller D, Vaya A, Aznar J, Ware R, Cruz NS, Lindner TH, Herrmann H, Reis A, Sperling K. (2002) Mutations in the Lamin B receptor gene produce an altered granulocyte nuclear morphology in humans (Pelger Huet Anomaly). Nature Genet 31: 410-414.
Olins, D. E., A. L. Olins, H. A. Levy, R. C. Durfee, S. M. Margle, E. P. Tinnel, and S. D. Dover (1983) Electron microscope tomography: Transcription in 3-D. Science 220, 498-500, cover.
Olins, A. L., and D. E. Olins (1974) Spheroid chromatin units (nu bodies). Science 183: 330-332.
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