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In this issue of Trends in Neurosciences, David Vinson and Ian Maze outline emerging evidence that monoamine neurotransmitters―long recognized for their roles as extracellular messengers in both adaptive and maladaptive brain plasticity―also covalently modify intracellular proteins at glutamine residues through a process termed monoaminylation. Such phenomena directly impact protein signaling cascades and gene expression, the latter occurring via modifications of histone proteins (often in combination with adjacent lysine methylation 'marks’) in both brain and peripheral systems; disruptions to these processes, in turn, contribute to numerous neurological disorders. Inspired by similarities between amino acid and playing card nomenlature, in the cover illustration, the King (K, lysine) is ’marked’ by a tri-partite fleur de lis – alluding to tri-methylation, and the Queen (Q, glutamine) is holding two flowers, reminiscent of the aromatic rings of monoamines.
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.
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.
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.
This could have been a cover for Ho and Treisman from NYU/Skirball. It was not selected.
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 Shimada et al. from Roeder Lab at Rockefeller. It was not selected.
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 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.
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.
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.)
This could have been a cover for Josefowicz et al. from Allis Lab at Rockefeller. It was not selected.
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).
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.
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.
This is not strictly a cover, but still a cool image that ended up printed in Medicine Iowa journal.
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