"A de novo sequence variant in Barrier-to-Autointegration Factor Is associated with dominant motor neuronopathy" - Last month, we helped the Geyer and Zinn-Justin labs run a few Western blots to document histone modification changes associated with a unique point mutation in Barrier-to-Autoinregration Factor (BAF) protein. The story is now available online! Congratulations to all who contributed to this collaboration!
"Dual role of lipids for genome stability and pluripotency facilitates full potency of mouse embryonic stem cells" - What started as a number of puzzling observations about how lipid supplements affect pluripotency circuit in culture, is now hot off the press at Protein & Cell - highlighting how deeply metabolic regulation is connected to genome integrity, epigenetic mechanisms, and whole organism development. Congratulations to all authors, and special kudos to Liangwen and Duancheng!
"Every amino acid matters, but people matter more" - the work of C. David Allis rewrote the textbook on how gene expression is regulated, but to everyone lucky to have known him personally, his impact extended far beyond fundamental discoveries. Dave's optimism and infectious excitement for science paired uniquely with a humble and gentle personality. Seemingly random souvenirs and photos of family and lab members past and present (the "lab family" term was used often) covered his office floor to ceiling, and brought more joy to him than his (well deserved) Nike of Samothrace. Colors of chromatin shine less brightly today, but his legacy will live on.
Feb 16 addendum - obituaries now published by Nature, Science and Cell offer a glimpse into how Dave's lab transformed the field.
New Lab Member:
Cameron joins the lab! It takes special courage to be the first employee - when scientific challenges are overshadowed by organizational ones. Welcome!
A fantastic story by Yadira Soto-Feliciano, Francisco Sanchez-Rivera, and many great collaborators in the Allis, Lowe and Armstrong labs is finally out in Cancer Discovery! One step closer to understanding the (non)redundancies of Mixed Lineage Leukemia methyltransferases, and how they can be leveraged in practical therapies for AML. Congratulations to Yadira and all!
As part of Interstellar Initiative, we have teamed up with Ankur Jain (Whitehead/MIT) and Noritaka Adachi (Tokyo Medical and Dental University) to study chromatin defects in Snyder-Robinson syndrome. Stay tuned for an update in a few months!
All* cells in human body carry same "blueprint" of genomic DNA, yet their phenotypes and functions are remarkably different - suggesting that genes are differentially regulated.
*exclusions apply, as always
Moreover, ~3.2 billion base pairs of DNA in every human cell* are folded into a nucleus - usually only a few microns in diameter - while preserving precise regulation of individual gene function. We aim to understand how this extraordinary level of compaction is achieved, and how, when misregulated, it drives human disease - from malignancy to developmental disorders.
We study gene regulation by H1 linker histones - small, dynamic proteins that contribute to both compaction of chromatin fiber (a complex of DNA and many nuclear proteins), and regulation of gene expression.
Alexey A. Soshnev
(...and your face could be here!)
Marcelot A, Rodriguez-Tirado F, Cuniasse P, Joiner M-l, Miron S, Soshnev AA, Fang M, Pufall MA, Mathews KD, Moore SA, Zinn-Justin S, Geyer PK. A De Novo Sequence Variant in Barrier-to-Autointegration Factor Is Associated with Dominant Motor Neuronopathy. Cells. 2023; 12(6):847. https://doi.org/10.3390/cells12060847
Zhong L, Gordillo M, Wang X, Qin Y, Huang Y, Soshnev AA, Kumar R, Nanjangud G, James D, Allis CD, Evans T, Carey B, Wen D. Dual role of lipids for genome stability and pluripotency facilitates full potency of mouse embryonic stem cells. Protein & Cell, Feb 16 2023, https://doi.org/10.1093/procel/pwad008
Soto-Feliciano YM, Sanchez-Rivera FJ, Perner F, Barrows DW, Kastenhuber ER, Ho Y-J, Carroll TS, Xiong Y, Anand D, Soshnev AA, Gates L, Beytagh MC, Cheon D, Gu CS, Liu XS, Krivtsov AV, Meneses M, de Stanchina E, Stone RM, Armstrong SA, Lowe SW, Allis CD. A molecular switch between mammalian MLL complexes dictates response to Menin-MLL inhibition. Cancer Disc, Oct 20 2022, https://doi.org/10.1158/2159-8290.CD-22-0416
Soshnev AA*, Allis CD, Cesarman E, Melnick AM*. Histone H1 mutations in lymphoma: a link(er) between chromatin organization, developmental reprogramming, and cancer. Cancer Res. 2021 Dec 15;81(24):6061-6070. PMID: 34580064 (*, corresponding author)
Yusufova N, Kloetgen A, Teater M, Osunsade A, Camarillo JM, Chin CR, Doane A, Venters BJ, Portillo-Ledesma S, Conway J, Philips J, Elemento O, Scott DW, Beguelin W, Licht JD, Kelleher N, Staudt LM, Skoultchi AI, Keogh MC, Apostolou E, Mason C, Imielinski M, Schlick T, David Y, Tsirigos A, Allis CD, Soshnev AA*, Cesarman E*, Melnick AM.* Histone H1 loss drives lymphoma by disrupting 3D chromatin architecture. Nature. 2021 Jan 14; 589(7841):299-305 PMID: 33299181 (*, corresponding author) - highlighted in Nature Reviews Genetics; highlighted in Cancer Discovery; recommended by F1000.
Phillips RE, Soshnev AA, Allis CD. Epigenomic Reprogramming as a Driver of Malignant Glioma. Cancer Cell. 2020 Nov 9;38(5):647-660. PMID: 32916125
Béguelin W, Teater M, Meydan C, Hoehn KB, Phillip JM, Soshnev AA, Venturutti L, Rivas MA, Calvo-Fernández MT, Gutierrez J, Camarillo JM, Takata K, Tarte K, Kelleher NL, Steidl C, Mason CE, Elemento O, Allis CD, Kleinstein SH, Melnick AM. Mutant EZH2 Induces a Pre-malignant Lymphoma Niche by Reprogramming the Immune Response. Cancer Cell. 2020 May 11; 37(5):655-673.e11. PMID: 32396861
Nacev BA, Feng L, Bagert JD, Lemiesz AE, Gao J, Soshnev AA, Kundra R, Schultz N, Muir TW, Allis CD. The expanding landscape of 'oncohistone' mutations in human cancers. Nature. 2019 Mar; 567(7749):473-478. PMID: 30894748.
Burdin DV, Kolobov AA, Brocker C, Soshnev AA, Samusik N, Demyanov AV, Brilloff S, Jarzebska N, Martens-Lobenhoffer J, Mieth M, Maas R, Bornstein SR, Bode-Boger SM, Gonzalez F, Weiss N, Rodionov RN. Diabetes-linked transcription factor HNF4α regulates metabolism of endogenous methylarginines and β-aminoisobutyric acid by controlling expression of alanine-glyoxylate aminotransferase 2. Sci Rep. 2016 Oct 18; 6:35503. PMID: 27752141
Soshnev AA*, Josefowicz SJ, Allis CD*. Greater than the sum of parts: the complexity of dynamic epigenome. Mol Cell. 2016 Jun 2;62(5):681-94. PMID: 27259201 (*, corresponding author).
Maze I, Wenderski W, Noh KM, Bagot RC, Tzavaras N, Purushothaman I, Elsässer SJ, Guo Y, Ionete C, Hurd YL, Tamminga CA, Halene T, Farrelly L, Soshnev AA, Wen D, Rafii S, Birtwistle MR, Akbarian S, Buchholz BA, Blitzer RD, Nestler EJ, Yuan ZF, Garcia BA, Shen L, Molina H, Allis CD. Critical Role of Histone Turnover in Neuronal Transcription and Plasticity. Neuron. 2015 Jul 1; 87(1):77-94. PMID: 26139371 (Highlighted in Neuron).
Maze I, Noh K-M, Soshnev AA, Allis CD. Every amino acid matters: essential contributions of histone variants to mammalian development and disease. Nat Rev Genet. 2014 Apr; 15(4):259-71. PMID: 24614311.
Barton LJ, Lovander KE, Ke W, Luttinger A, Soshnev AA, Geyer PK. Nuclear lamina dysfunction triggers a novel germline stem cell-specific checkpoint. Nat Commun. 2018 Sep 27; 9(1):3960. PMID: 30262885
Barton LJ, Soshnev AA, Geyer PK. Networking in the nucleus: A spotlight on LEM-domain proteins. Curr Opin Cell Biol, 2015 Apr 9; 34:1-8. PMID: 25863918 (Journal cover).
Soshnev AA, Baxley RM, Manak RJ, Tan K, Geyer PK. The insulator protein Suppressor of Hairy-wing is an essential transcriptional repressor in the Drosophila ovary. Development. 2013 Aug 13; 140, 3613-23. PMID: 23884443.
Hohl AM, Thompson M, Soshnev AA, Wu J, Morris J, Shih-Hsieh T, Wu CT, Geyer PK. Restoration of Topoisomerase 2 Function by Complementation of Defective Monomers in Drosophila. Genetics. 2012 Nov; 192(3):843-56. PMID: 22923380.
Soshnev AA, He B, Baxley RM, Jiang N, Hart CM, Tan K, Geyer PK. Genome-wide studies of the multi-zinc finger Drosophila Suppressor of Hairy-wing protein in the ovary. Nucleic Acids Res. 2012 Jul; 40(12):5415-31. PMID: 22406832.
Soshnev AA, Ishimoto H, McAllister BF, Li X, Wehling MD, Kitamoto T, Geyer PK. A conserved long non-coding RNA plays a role in sleep regulation in Drosophila. Genetics 2011 Oct 1; 189(2):455-468. PMID: 21775470 (Highlighted article).
Baxley RM, Soshnev AA, Koryakov DE, Zhimulev IF, Geyer PK. The role of the Suppressor of Hairy-wing insulator protein in Drosophila oogenesis. Dev Biol. 2011 Aug 15; 356(2):398-410. PMID: 21651900 (Journal cover).
Soshnev AA*, Li X*, Wehling MD, Geyer PK. Context differences reveal insulator and activator functions of a Su(Hw) binding region. PLoS Genet. 2008 Aug 15;4(8):e1000159. PMID: 18704163 (*, contributed equally).
Semiglazov VF, Aĭlamazian EK, Baĭliuk EN, Niauri DA, Ivanov VG, Manikhas AG, Kvetnoĭ IM, Soshnev AA. [Prophylaxis of breast cancer in patients with hyperproliferative disorders of the reproductive system] Vopr Onkol. 2006;52(3):247-57. In Russian. PMID: 17191696.
Alexey A. Soshnev
(210) 458-7950 (office)
(210) 458-7951 (lab)
Department of Neuroscience, Developmental and Regenerative Biology
University of Texas at San Antonio
One UTSA Circle
San Antonio, TX 78249
#sciart - some hits and a few misses we are still proud of:
This could have been a cover for our Cancer Cell review on epigenetic misregulation in glioma. It was not selected.
This could have been a cover for Ho and Treisman from NYU/Skirball. It was not selected.
This could have been a cover for Finkin et al from Nussenzweig Lab at Rockefeller. It was not selected.
This could have been a cover for Shimada et al. from Roeder Lab at Rockefeller. It was not selected.
This is not strictly a cover, but still a cool image that ended up printed in Medicine Iowa journal.