Mar9 2023

New Paper:

"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!

Feb 16 2023

New Paper:

"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! 

Jan 9 2023

in memoriam

"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.

Nov 1 2022

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!

Oct 24 2022

New Paper:

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!

Oct 12 2022

New Project:

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!

Research

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.

People

Alexey A. Soshnev

PI

Cameron Chapa

research associate

positions available!..

(...and your face could be here!)

Publications

at UTSA:


Postdoctoral:


Graduate:

Contact

Alexey A. Soshnev

alexey.soshnev(a)utsa.edu
(210) 458-7950 (office)
(210) 458-7951 (lab) 

@alexeysoshnev

Assistant Professor,
Department of Neuroscience, Developmental and Regenerative Biology

University of Texas at San Antonio

BSB 2.03.28

One UTSA Circle

San Antonio, TX 78249

USA

Journal covers

#sciart - some hits and a few misses we are still proud of: 

In this issue, Phillips, Soshnev and Allis discuss the epigenetic misregulation in gliomagenesis. Missense mutation of Histone H3 lysine 27 to methionine (H3 K27M) defines a class of pediatric gliomas and has become a textbook example of epigenetic driver in human malignancy. While H3 is encoded by fifteen paralog genes in humans, a single heterozygous mutation is sufficient to dominantly inhibit the enzymatic function of Polycomb Repressor Complex 2. The cover, printed with child wooden alphabet blocks, illustrates the identical amino acid sequences of the multiple copies of H3 (AARKSAPA, pastel colors), and dramatic effect of one missense substitution (M, in black) in this deadly malignancy.
This could have been a cover for our Cancer Cell review on epigenetic misregulation in glioma. It was not selected.
In this issue, Korb et al. (1209–1223) identified a subset of epigenetic regulators as potential targets in Fragile X syndrome. On the cover, the sagittal section of the human brain hemisphere is depicted using paper filigree, with contours of the anatomical structures outlined with artistic representation of the “chromatin fiber.” The repeat units of core histones are shown in canonical red, green, blue, and yellow colors, with linker DNA in teal. The parallel between chromatin architecture and cortical folding highlights the emerging role of epigenetic misregulation in human neurological disorders. 
This could have been a cover for  Hoffmann and Sanchez-Rivera et al @ Rice/Lowe Labs. It was not selected, but we still like the colors!
The artwork shows increased synaptic contacts on a larger muscle relative to a smaller one, driven by signaling from the growing muscle to the presynaptic motor neuron. The muscles are depicted as buildings, with the larger one receiving more connections from the city grid. Scene is inspired by the authors' experience during the COVID-19 shutdown in New York City. 
This could have been a cover for  Ho and Treisman from NYU/Skirball. It was not selected.
In this issue, Finkin et al. report that MYC, induced by follicular helper T-cells during affinity maturation in the germinal center, is a critical determinant of B cell division capacity. Rapid cell divisions require a reservoir of essential metabolites to sustain S-G2-M cycling. Light zone MYC expression regulates metabolite accumulation and B cell growth, dictating the subsequent dark zone cell divisions. A mosaic of different size beads represents diverse cellular composition of the germinal center, where largest beads, spelling out “MYC”, are the clones primed for expansion due to MYC accumulation.
This could have been a cover for Finkin et al from Nussenzweig Lab at Rockefeller. It was not selected.
PHF6 controls the phenotypic state of B-cell leukemia cells by regulating the expression of lineage-specific genes. Shown here is a histological analysis of the two distinct lymphoid diseases that are formed in the presence (left) or absence (right) of PHF6. The different ontologies of these malignancies are explained by drastic changes in the expression of genes that regulate the function of normal B and T cells. Mechanistically, PHF6 promotes transcription factor accessibility to B-cell-specific genes in leukemia cells while blocking access to T-cell-specific genes. (For details, see Soto-Feliciano et al., p. 973.) 
Hematopoietic stem cells give rise to an array of differentiated cell types that function in innate and adaptive  immunity.  To serve their  respective functions, these cells must in turn  respond to a vast number of environmental  cues that initiate programs leading  to proliferation, differentiation and effector   function. The myriad of cell fate decisions   that   must occur involve changes in gene expression   that are mediated by transcription factors,  epigenetics, enhancers, genome organization,  long non-coding RNAs and post-transcriptional  regulation. This volume of Immunological  Reviews, guest edited by Amy Weinmann who is an expert in the field, presents a compendium of reviews that seek to put these regulatory mechanisms in perspective.
Revival of trade - exchange of goods - heralded the end of the Dark Ages in Europe, bringing upon the intellectual awaking of the Renaissance. Likewise, global and local histone turnover is shaping cell-type specific functions in the nervous system, critical for neurological plasticity and cognition, disruptions of which result in disease and intellectual decline, as described by Wenderski and Maze. Original artwork based on illumination from the 15th century Trattato de Arithmetica, depicting two merchants engaged in (histone) barter transaction, with histone H3/H4 dimer and nucleosome structures depicted (PDB structures 2HUE and AOI1, respectively). 
Shimada et al. demonstrate that linker histone H1-mediated repression of compacted chromatin involves abrogation of histone acetyltransferase p300 enzymatic activity, whereas gene-specific eviction of H1 by p300-bound chaperone NAP1 facilitates p300-dependent core histone acetylation and transcriptional activation. On the cover, histone chaperones and p300 are shown as Lego figures, operating on the repressive (top - grey, black and blue blocks) and active (bottom - red, orange and yellow blocks) chromatin - reminiscent of traditional heat map representation of genomic regions.
This could have been a cover for Shimada et al. from Roeder Lab at Rockefeller. It was not selected. 
This could have been a cover for Josefowicz et al. from Allis Lab at Rockefeller. It was not selected. 
The cover shows a whole-mount Drosophila ovary, immunostained for fibrillarin (red), Su(Hw) (green) and counterstained with DAPI (blue). Defects in nucleolar structure in su(Hw)f/v ovaries do not affect ribosome biogenesis or oocyte production, implying that the absence of structural reorganization of NC chromosomes is not responsible for sterility of su(Hw) mutant females. 
The cover shows a Google Map of the nucleus, highlighting organizational features covered by review articles included in this issue. Zooming into the nuclear periphery it shows features of the nuclear envelope and the contiguous endoplasmic reticulum. Green and red roadways depict chromosomal regions harboring genes of different transcriptional activity. The road construction sign denotes a chromosomal region undergoing DNA repair. Colored squares and circles indicate locations of architectural landmarks or enrichments of organizing proteins, such as chromatin lamina-associated domains (LADs), the nuclear lamina, LEM-domain proteins (LEM-D), Barrier-to-Autointegration Factor (BAF), and Cajal bodies. The wilderness region encompasses the nucleolus. Ferry lines connected to US highways indicate nuclear import and export that includes transit through nuclear pores. The subway symbol (blue square) represents long distance chromosomal loops mediated by protein complexes, such as condensins. 
Inspired by the Space Invaders arcade game, the relationship between Torso signaling (aliens), nuclear envelope, and Germ Cell-Less (GCL; laser cannon) is depicted. When the nuclear envelope breaks down (shown on the right), GCL targets Torso for degradation at the plasma membrane, suppressing somatic cell lineages and promoting the formation of primordial germ cells. The background image is a stylized micrograph showing GCL (magenta) at the nuclear envelope in pre-mitotic cells (left) and at the plasma membrane in the dividing cells (right). For more, see Pae et al., pp. 130–142.  
Alternative cover for Pae et al (Lehmann Lab at Skirball/NYU). Another version was selected, so we still count it as a win.
A confocal image shows the expression pattern of transcription factors Centrosomal protein 190 (CP190) and Suppressor of Hairy-wing [Su(Hw)]—visible in red and green, respectively—in a fruit fly embryo. Pamela Geyer, PhD, professor of bio-chemistry, and obstetrics and gynecology, uses this model to show how these two proteins collaborate to establish DNA regulatory elements known as chromatin insulators during development, including in the early embryo. Better understanding of chromatin uinsulators could improve strategies for gene therapy and treatment of human disease.
This is not strictly a cover, but still a cool image that ended up printed in Medicine Iowa journal.