scholarly journals Establishment and function of chromatin modification at enhancers

Open Biology ◽  
2020 ◽  
Vol 10 (10) ◽  
pp. 200255
Author(s):  
Amanuel Tafessu ◽  
Laura A. Banaszynski
Keyword(s):  
Chromatin Modification ◽  
Cell Types ◽  
Histone Variants ◽  
Cell Fates ◽  
Chromatin Signature ◽  
Post Translational Modifications ◽  
Single Genome ◽  
Distinct Cell ◽  
Condensate Formation ◽  
And Function

How a single genome can give rise to distinct cell types remains a fundamental question in biology. Mammals are able to specify and maintain hundreds of cell fates by selectively activating unique subsets of their genome. This is achieved, in part, by enhancers—genetic elements that can increase transcription of both nearby and distal genes. Enhancers can be identified by their unique chromatin signature, including transcription factor binding and the enrichment of specific histone post-translational modifications, histone variants, and chromatin-associated cofactors. How each of these chromatin features contributes to enhancer function remains an area of intense study. In this review, we provide an overview of enhancer-associated chromatin states, and the proteins and enzymes involved in their establishment. We discuss recent insights into the effects of the enhancer chromatin state on ongoing transcription versus their role in the establishment of new transcription programmes, such as those that occur developmentally. Finally, we highlight the role of enhancer chromatin in new conceptual advances in gene regulation such as condensate formation.

scholarly journals An opaque cell-specific expression program of secreted proteases and transporters allows cell-type cooperation in Candida albicans

2020 ◽  
Author(s):  
Matthew B. Lohse ◽  
Lucas R. Brenes ◽  
Naomi Ziv ◽  
Michael B. Winter ◽  
Charles S. Craik ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Nitrogen Source ◽  
Cell Types ◽  
Mixed Cultures ◽  
Sole Nitrogen Source ◽  
Peptide Transporters ◽  
Single Genome ◽  
Distinct Cell ◽  
Reference Number ◽  
Secreted Proteases

AbstractAn unusual feature of the opportunistic pathogen C. albicans is its ability to stochastically switch between two distinct, heritable cell types called white and opaque. Here, we show that only opaque cells, in response to environmental signals, massively up-regulate a specific group of secreted proteases and peptide transporters, allowing exceptionally efficient use of proteins as sources of nitrogen. We identify the specific proteases (members of the secreted aspartyl protease (SAP) family) needed for opaque cells to proliferate under these conditions, and we identify four transcriptional regulators of this specialized proteolysis and uptake program. We also show that, in mixed cultures, opaque cells enable white cells to also proliferate efficiently when proteins are the sole nitrogen source. Based on these observations, we suggest that one role of white-opaque switching is to create mixed populations where the different phenotypes derived from a single genome are shared between two distinct cell types.SummaryThe opportunistic human fungal pathogen Candida albicans switches between two distinct, heritable cell types, named “white” and “opaque.” We show that opaque cells, in response to proteins as the sole nitrogen source, up-regulate a specialized program, including specific secreted aspartyl proteases and peptide transporters. We demonstrate that, in mixed cultures, opaque cells enable white cells to respond and proliferate more efficiently under these conditions. These observations suggest that white-opaque switching creates mixtures of cells where the population characteristics - which derive from a single genome - reflect the contributions of two distinct cell types.Dataset Reference NumbersThe .RAW files for both sets of Mass Spectrometry experiments have been deposited at the ProteoSAFe resource (https://proteomics.ucsd.edu/ProteoSAFe/).MSP-MS experiment reference number: MSV000085279. For reviewer access use login “MSV000085279_reviewer” and password “candidamspms”.Proteomics experiment reference number: MSV000085283. For reviewer access use login “MSV000085283_reviewer” and password “candidaprot”.

scholarly journals High Resolution Single Cell Maps Reveals Distinct Cell Organization and Function Across Different Regions of the Human Intestine

2021 ◽  
Author(s):  
John W Hickey ◽  
Winston R Becker ◽  
Stephanie A Nevins ◽  
Aaron M Horning ◽  
Almudena Espin Perez ◽  
...  
Keyword(s):  
Single Cell ◽  
Immune Surveillance ◽  
Cell Types ◽  
Open Chromatin ◽  
Specific Cell ◽  
Symbiotic Relationships ◽  
Distinct Cell ◽  
Cell Organization ◽  
Reference Map ◽  
And Function

The colon is a complex organ that promotes digestion, extracts nutrients, participates in immune surveillance, maintains critical symbiotic relationships with microbiota, and affects overall health. To better understand its organization, functions, and its regulation at a single cell level, we performed CODEX multiplexed imaging, as well as single nuclear RNA and open chromatin assays across eight different intestinal sites of four donors. Through systematic analyses we find cell compositions differ dramatically across regions of the intestine, demonstrate the complexity of epithelial subtypes, and find that the same cell types are organized into distinct neighborhoods and communities highlighting distinct immunological niches present in the intestine. We also map gene regulatory differences in these cells suggestive of a regulatory differentiation cascade, and associate intestinal disease heritability with specific cell types. These results describe the complexity of the cell composition, regulation, and organization for this organ, and serve as an important reference map for understanding human biology and disease.

scholarly journals An Opaque Cell-Specific Expression Program of Secreted Proteases and Transporters Allows Cell-Type Cooperation in Candida albicans

Genetics ◽  
2020 ◽  
Vol 216 (2) ◽  
pp. 409-429
Author(s):  
Matthew B. Lohse ◽  
Lucas R. Brenes ◽  
Naomi Ziv ◽  
Michael B. Winter ◽  
Charles S. Craik ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Opportunistic Pathogen ◽  
Cell Types ◽  
Specific Expression ◽  
Environmental Signals ◽  
Single Genome ◽  
Distinct Cell ◽  
Secreted Proteases ◽  
Expression Program

An unusual feature of the opportunistic pathogen Candida albicans is its ability to switch stochastically between two distinct, heritable cell types called white and opaque. Here, we show that only opaque cells, in response to environmental signals, massively upregulate a specific group of secreted proteases and peptide transporters, allowing exceptionally efficient use of proteins as sources of nitrogen. We identify the specific proteases [members of the secreted aspartyl protease (SAP) family] needed for opaque cells to proliferate under these conditions, and we identify four transcriptional regulators of this specialized proteolysis and uptake program. We also show that, in mixed cultures, opaque cells enable white cells to also proliferate efficiently when proteins are the sole nitrogen source. Based on these observations, we suggest that one role of white-opaque switching is to create mixed populations where the different phenotypes derived from a single genome are shared between two distinct cell types.

scholarly journals Editorial—Role of DNA Methyltransferases in the Epigenome

Genes ◽  
2019 ◽  
Vol 10 (8) ◽  
pp. 574 ◽  
Author(s):  
Jeltsch ◽  
Gowher
Keyword(s):  
Dna Methylation ◽  
Phenotypic Diversity ◽  
Rapid Development ◽  
Cell Types ◽  
Dna Methyltransferases ◽  
Mammalian Development ◽  
Exciting Field ◽  
Post Translational Modifications ◽  
And Function ◽  
Future Work

DNA methylation, a modification found in most species, regulates chromatin functions in conjunction with other epigenome modifications, such as histone post-translational modifications and non-coding RNAs. In mammals, DNA methylation has essential roles in development by orchestrating the generation and maintenance of the phenotypic diversity of human cell types. This Special Issue of Genes contains eight review articles, which cover several aspects of epigenome regulation by DNA methyltransferases (DNMTs), the enzymes responsible for the introduction of DNA methylation. The manuscripts present the most recent advances regarding the structure and function of DNMTs, their targeting and regulation by interacting factors and chromatin modifications, and the roles of DNMTs in mammalian development and human diseases. However, many aspects of these important enzymes are still insufficiently understood. Potential directions of future work are the regulation of DNMTs by post-translational modifications and their connection to cellular signaling and second messenger cascades on one hand and to large multifactorial epigenetic chromatin circuits on the other. Additionally, technical advancements, including the availability of designer nucleosomes and the rapid development of cryo-electron microscopy are expected to trigger breakthrough discoveries in this exciting field.

scholarly journals Biophysical Support for Functionally Distinct Cell Types in the Frontal Eye Field

2009 ◽  
Vol 101 (2) ◽  
pp. 912-916 ◽  
Author(s):  
Jeremiah Y. Cohen ◽  
Pierre Pouget ◽  
Richard P. Heitz ◽  
Geoffrey F. Woodman ◽  
Jeffrey D. Schall
Keyword(s):  
Action Potentials ◽  
Cell Types ◽  
Frontal Eye Field ◽  
Subcortical Structures ◽  
Brain Areas ◽  
Visual Neurons ◽  
Distinct Cell ◽  
Eye Field ◽  
And Function ◽  
Different Cell Types

Numerous studies have described different functional cell types in the frontal eye field (FEF), but the reliability of the distinction between these types has been uncertain. Studies in other brain areas have described specific differences in the width of action potentials recorded from different cell types. To substantiate the functionally defined cell types encountered in FEF, we measured the width of spikes of visual, movement, and visuomovement types of FEF neurons in macaque monkeys. We show that visuomovement neurons had the thinnest spikes, consistent with a role in local processing. Movement neurons had the widest spikes, consistent with their role in sending eye movement commands to subcortical structures such as the superior colliculus. Visual neurons had wider spikes than visuomovement neurons, consistent with their role in receiving projections from occipital and parietal cortex. These results show how structure and function of FEF can be linked to guide inferences about neuronal architecture.

The functional anatomy of the digestive tract of a shrimp Metapenaeus bennettae Racek & Dall (Crustacea : Decapoda : Penaeidae)

1967 ◽  
Vol 15 (4) ◽  
pp. 699 ◽  
Author(s):  
W Dall
Keyword(s):  
Digestive Gland ◽  
Functional Anatomy ◽  
Cell Types ◽  
Peritrophic Membrane ◽  
Additional Function ◽  
Abdominal Somite ◽  
Distinct Cell ◽  
Secretory Type ◽  
And Function ◽  
Intrinsic Muscles

The anatomy of the proventriculus, digestive gland, midgut and its diverticula, and the rectum is described. In structure and function the proventriculus is similar to that of anumber of other Decapoda. Two distinct cell types occur in the digestive gland, a secretory type, and a mucopolysaccharide-containing type, whose function is not clear. The digestive gland has no intrinsic muscles, and depends on extrinsic muscles, and possibly ingested water, for filling and emptying. The midgut extends to the sixth abdominal somite and faecal material is contained in a peritrophic membrane. Evidence for secretory functions of the midgut and anterior and posterior diverticula is discussed. The rectal lining is formed into six longitudinal pads which are used to expel long sections of peritrophic membrane containing faeces. Methods of feeding are described. Permeability of the anterior proventriculus to 22Na and [14C] glucose was measured; 22Na approached equilibrium in 6-7 hr, but [14C] glucose passed through at about one-seventh this rate, indicating that direct glucose uptake from the proventriculus would be negligible. Food, labelled with particulate ll0Ag, was found to begin leaving the proventriculus almost as soon as it was filled, but complete emptying took 6-12 hr. Defecation was at a peak 5-8 hr after food ingestion, but continued up to 20 hr. The rectum appears to have the additional function of pumping water into the gut via the anus.

scholarly journals On the edge: Evolution of polarity protein BASL and the capacity for stomatal lineage asymmetric divisions

2021 ◽  
Author(s):  
Ido Nir ◽  
Gabriel O Amador ◽  
Yan Gong ◽  
Nicole K Smoot ◽  
Le Cai ◽  
...  
Keyword(s):  
Cell Fate ◽  
Cell Types ◽  
Cell Fates ◽  
Division Plane ◽  
Asymmetric Cell Divisions ◽  
Cell Divisions ◽  
Distinct Cell ◽  
Asymmetric Divisions ◽  
Stem Cell Divisions ◽  
Stomatal Lineage

Asymmetric and oriented stem cell divisions enable the continued production of patterned tissues. The molecules that guide these divisions include several polarity proteins that are localized to discrete plasma membrane domains, are differentially inherited during asymmetric divisions, and whose scaffolding activities can guide division plane orientation and subsequent cell fates. In the stomatal lineages on the surfaces of plant leaves, asymmetric and oriented divisions create distinct cell types in physiologically optimized patterns. The polarity protein BASL is a major regulator of stomatal lineage division and cell fate asymmetries in Arabidopsis, but its role in the stomatal lineages of other plants was unclear. Here, using phylogenetic and functional assays, we demonstrate that BASL is a dicot specific polarity protein. Among dicots, divergence in BASLs roles may reflect some intrinsic protein differences, but more likely reflects previously unappreciated differences in how asymmetric cell divisions are employed for pattern formation in different species. This multi-species analysis therefore provides insight into the evolution of a unique polarity regulator and into the developmental choices available to cells as they build and pattern tissues.

scholarly journals spalt-dependent switching between two cell fates that are induced by the Drosophila EGF receptor

Development ◽  
2001 ◽  
Vol 128 (5) ◽  
pp. 723-732 ◽  
Author(s):  
P.R. Elstob ◽  
V. Brodu ◽  
A.P. Gould
Keyword(s):  
Cell Fate ◽  
Animal Species ◽  
Egf Receptor ◽  
Zinc Finger Protein ◽  
Cell Types ◽  
Chordotonal Organ ◽  
Egfr Signaling ◽  
Cell Fates ◽  
Finger Protein ◽  
Distinct Cell

Signaling from the EGF receptor (EGFR) can trigger the differentiation of a wide variety of cell types in many animal species. We have explored the mechanisms that generate this diversity using the Drosophila peripheral nervous system. In this context, Spitz (SPI) ligand can induce two alternative cell fates from the dorsolateral ectoderm: chordotonal sensory organs and non-neural oenocytes. We show that the overall number of both cell types that are induced is controlled by the degree of EGFR signaling. In addition, the spalt (sal) gene is identified as a critical component of the oenocyte/chordotonal fate switch. Genetic and expression analyses indicate that the SAL zinc-finger protein promotes oenocyte formation and supresses chordotonal organ induction by acting both downstream and in parallel to the EGFR. To explain these findings, we propose a prime-and-respond model. Here, sal functions prior to signaling as a necessary but not sufficient component of the oenocyte prepattern that also serves to raise the apparent threshold for induction by SPI. Subsequently, sal-dependent SAL upregulation is triggered as part of the oenocyte-specific EGFR response. Thus, a combination of SAL in the responding nucleus and increased SPI ligand production sets the binary cell-fate switch in favour of oenocytes. Together, these studies help to explain how one generic signaling pathway can trigger the differentiation of two distinct cell types.

scholarly journals Maintenance of Cell Fates by Regulation of the Histone Variant H3.3 in Caenorhabditis elegans

2018 ◽  
Author(s):  
Yukimasa Shibata ◽  
Kiyoji Nishiwaki
Keyword(s):  
Caenorhabditis Elegans ◽  
Cell Fate ◽  
Binding Protein ◽  
Ectopic Expression ◽  
Cell Types ◽  
Histone Variants ◽  
Histone Variant ◽  
Histone H4 ◽  
Cell Fates ◽  
Selector Genes

HighlightsTLK-1 maintains cell fates by repression of selector genesTLK-1 and downstream H3 chaperone CAF1 inhibit H3.3 depositionLoss of sin-3 suppresses the defect in cell-fate maintenance of tlk-1 mutantsAcH4-binding protein BET-1 is necessary for sin-3 suppressionSummaryCell-fate maintenance is important to preserve the variety of cell types that are essential for the formation and function of tissues. We previously showed that the acetylated histone H4-binding protein BET-1 maintains cell fate by recruiting the histone variant H2A.z. Here, we report that Caenorhabditis elegans tousled-like kinase TLK-1 and the histone H3 chaperone CAF1 maintain cell fate by preventing the incorporation of histone variant H3.3 into nucleosomes, thereby repressing ectopic expression of transcription factors that induce cell-fate specification. Genetic analyses suggested that TLK-1 and BET-1 act in parallel pathways. In tlk-1 mutants, the loss of SIN-3, which promotes histone acetylation, suppressed a defect in cell-fate maintenance in a manner dependent on MYST family histone acetyltransferase MYS-2 and BET-1. sin-3 mutation also suppressed abnormal H3.3 incorporation. Thus, we propose that the regulation and interaction of histone variants play crucial roles in cell-fate maintenance through the regulation of selector genes.

Fine Structure of the Malpighian Tubules of the Mosquito, Culex pipiens

1971 ◽  
Vol 29 ◽  
pp. 402-403
Author(s):  
Brendan Clifford
Keyword(s):  
Fine Structure ◽  
Culex Pipiens ◽  
Stellate Cell ◽  
Malpighian Tubule ◽  
Cell Types ◽  
Instar Larva ◽  
Malpighian Tubules ◽  
Calliphora Erythrocephala ◽  
Distinct Cell ◽  
Basal Plasma

An ultrastructural investigation of the Malpighian tubules of the fourth instar larva of Culex pipiens was undertaken as part of a continuing study of the fine structure of transport epithelia.Each of the five Malpighian tubules was found to be morphologically identical and regionally undifferentiated. Two distinct cell types, the primary and stellate, were found intermingled along the length of each tubule. The ultrastructure of the stellate cell was previously described in the Malpighian tubule of the blowfly, Calliphora erythrocephala by Berridge and Oschman.The basal plasma membrane of the primary cell is extremely irregular, giving rise to a complex interconnecting network of basal channels. The compartments of cytoplasm entrapped within this system of basal infoldings contain mitochondria, free ribosomes, and small amounts of rough endoplasmic reticulum. The mitochondria are distinctive in that the cristae run parallel to the long axis of the organelle.

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