PHF8 histone demethylase regulates astrocyte differentiation and function

Epigenetic factors have been shown to play a crucial role in X-linked intellectual disability (XLID). Here, we investigate the contribution of the XLID-associated histone demethylase PHF8 to astrocyte differentiation and function. Using genome-wide analyses and biochemical assays, we reveal a regulatory crosstalk between PHF8 and Notch signaling pathway that balances the expression of the master astrocytic gene Nfia. Moreover, PHF8 regulates key synaptic genes in astrocytes by keeping low levels of H4K20me3. Accordingly, astrocytic-PHF8 depletion has a striking effect on neuronal synapse formation and maturation in vitro. These data reveal that PHF8 is crucial in astrocyte development to maintain the chromatin homeostasis and limiting the heterochromatin formation at synaptogenic genes. Our studies suggest a new paradigm for the implication of epigenetics in intellectual disability.

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Biomimetic human small muscular pulmonary arteries

Science Advances ◽

10.1126/sciadv.aaz2598 ◽

2020 ◽

Vol 6 (13) ◽

pp. eaaz2598 ◽

Cited By ~ 1

Author(s):

Qianru Jin ◽

Anil Bhatta ◽

Jayson V. Pagaduan ◽

Xing Chen ◽

Hoku West-Foyle ◽

...

Keyword(s):

Pulmonary Arteries ◽

In Vitro Models ◽

Structure And Function ◽

Nitric Oxide Production ◽

New Paradigm ◽

Public Health Challenge ◽

Pulmonary Arterial ◽

Spatial Positioning ◽

And Function

Changes in structure and function of small muscular arteries play a major role in the pathophysiology of pulmonary hypertension, a burgeoning public health challenge. Improved anatomically mimetic in vitro models of these microvessels are urgently needed because nonhuman vessels and previous models do not accurately recapitulate the microenvironment and architecture of the human microvascular wall. Here, we describe parallel biofabrication of photopatterned self-rolled biomimetic pulmonary arterial microvessels of tunable size and infrastructure. These microvessels feature anatomically accurate layering and patterning of aligned human smooth muscle cells, extracellular matrix, and endothelial cells and exhibit notable increases in endothelial longevity and nitric oxide production. Computational image processing yielded high-resolution 3D perspectives of cells and proteins. Our studies provide a new paradigm for engineering multicellular tissues with precise 3D spatial positioning of multiple constituents in planar moieties, providing a biomimetic platform for investigation of microvascular pathobiology in human disease.

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Inhibition of lysine-specific histone demethylase 1A results in meiotic aberration during oocyte maturation in vitro in goats

Theriogenology ◽

10.1016/j.theriogenology.2019.12.011 ◽

2020 ◽

Vol 143 ◽

pp. 168-178 ◽

Cited By ~ 1

Author(s):

Zifei Liu ◽

Guomin Zhang ◽

Mingtian Deng ◽

Hua Yang ◽

Jing Pang ◽

...

Keyword(s):

Oocyte Maturation ◽

Histone Demethylase ◽

Maturation In Vitro

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An H3K9 methylation-dependent protein interaction regulates the non-enzymatic functions of a putative histone demethylase

eLife ◽

10.7554/elife.53155 ◽

2020 ◽

Vol 9 ◽

Cited By ~ 1

Author(s):

Gulzhan Raiymbek ◽

Sojin An ◽

Nidhi Khurana ◽

Saarang Gopinath ◽

Ajay Larkin ◽

...

Keyword(s):

Protein Interaction ◽

Histone Demethylase ◽

H3k9 Methylation ◽

Heterochromatin Formation ◽

Protein Protein Interaction ◽

Enzymatic Function ◽

C Terminus ◽

Jmjc Domain

H3K9 methylation (H3K9me) specifies the establishment and maintenance of transcriptionally silent epigenetic states or heterochromatin. The enzymatic erasure of histone modifications is widely assumed to be the primary mechanism that reverses epigenetic silencing. Here, we reveal an inversion of this paradigm where a putative histone demethylase Epe1 in fission yeast, has a non-enzymatic function that opposes heterochromatin assembly. Mutations within the putative catalytic JmjC domain of Epe1 disrupt its interaction with Swi6HP1 suggesting that this domain might have other functions besides enzymatic activity. The C-terminus of Epe1 directly interacts with Swi6HP1, and H3K9 methylation stimulates this protein-protein interaction in vitro and in vivo. Expressing the Epe1 C-terminus is sufficient to disrupt heterochromatin by outcompeting the histone deacetylase, Clr3 from sites of heterochromatin formation. Our results underscore how histone modifying proteins that resemble enzymes have non-catalytic functions that regulate the assembly of epigenetic complexes in cells.

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Neurotrophin signaling among neurons and glia during formation of tripartite synapses

Neuron Glia Biology ◽

10.1017/s1740925x05000189 ◽

2004 ◽

Vol 1 (4) ◽

pp. 339-349 ◽

Cited By ~ 25

Author(s):

SARINA B. ELMARIAH ◽

ETHAN G. HUGHES ◽

EUN JOO OH ◽

RITA J. BALICE-GORDON

Keyword(s):

Gabaa Receptor ◽

Molecular Mechanisms ◽

Synapse Formation ◽

Synaptic Modulators ◽

Central Synapses ◽

Receptor Clusters ◽

And Function ◽

Neurotrophin Signaling

Synapse formation in the CNS is a complex process that involves the dynamic interplay of numerous signals exchanged between pre- and postsynaptic neurons as well as perisynaptic glia. Members of the neurotrophin family, which are widely expressed in the developing and mature CNS and are well-known for their roles in promoting neuronal survival and differentiation, have emerged as key synaptic modulators. However, the mechanisms by which neurotrophins modulate synapse formation and function are poorly understood. Here, we summarize our work on the role of neurotrophins in synaptogenesis in the CNS, in particular the role of these signaling molecules and their receptors, the Trks, in the development of excitatory and inhibitory hippocampal synapses. We discuss our results that demonstrate that postsynaptic TrkB signaling plays an important role in modulating the formation and maintenance of NMDA and GABAA receptor clusters at central synapses, and suggest that neurotrophin signaling coordinately modulates these receptors as part of mechanism that promotes the balance between excitation and inhibition in developing circuits. We also discuss our results that demonstrate that astrocytes promote the formation of GABAergic synapses in vitro by differentially regulating the development of inhibitory presynaptic terminals and postsynaptic GABAA receptor clusters, and suggest that glial modulation of inhibitory synaptogenesis is mediated by neurotrophin-dependent and -independent signaling. Together, these findings extend our understanding of how neuron–glia communication modulates synapse formation, maintenance and function, and set the stage for defining the cellular and molecular mechanisms by which neurotrophins and other cell–cell signals direct synaptogenesis in the developing brain.

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Exposure of Female Macaques to Western-Style Diet With or Without Chronic T In Vivo Alters Secondary Follicle Function During Encapsulated 3-Dimensional Culture

Endocrinology ◽

10.1210/en.2014-1711 ◽

2015 ◽

Vol 156 (3) ◽

pp. 1133-1142 ◽

Cited By ~ 10

Author(s):

Jing Xu ◽

Whitney K. McGee ◽

Cecily V. Bishop ◽

Byung S. Park ◽

Judy L. Cameron ◽

...

Keyword(s):

The Body ◽

Fat Percentage ◽

Ctrl Group ◽

3 Dimensional ◽

Antral Follicles ◽

Maturation In Vitro ◽

And Function ◽

Endothelial Growth Factor

Abstract Increased adiposity and hyperandrogenemia alter reproductive parameters in both animal models and women, but their effects on preantral follicles in the ovary remain unknown. We recently reported that Western-style diet (WSD) consumption over 1 year, with or without chronic exposure to elevated circulating T, increased the body fat percentage, elicited insulin resistance, suppressed estradiol and progesterone production, as well as altered the numbers, size, and dynamics of antral follicles in the ovary during the menstrual cycle in female macaques. Therefore, experiments were designed to compare the WSD and WSD+T effects to age-matched controls on the survival, growth, and function of isolated secondary follicles during 5 weeks of encapsulated 3-dimensional culture. Follicle survival significantly declined in the WSD and WSD+T groups compared with the control (CTRL) group. Although media progesterone levels were comparable among groups, androstenedione and estradiol levels were markedly reduced in the WSD and WSD+T groups compared with the CTRL group at week 5. Anti-Müllerian hormone levels peaked at week 3 and were lower in the WSD+T group compared with the WSD or CTRL group. Vascular endothelial growth factor levels also decreased at week 5 in the WSD+T group compared with the WSD or CTRL group. After human chorionic gonadotropin exposure, only antral follicles developed from the CTRL group yielded metaphase II oocytes. Thus, WSD with or without T exposure affects the cohort of secondary follicles in vivo, suppressing their subsequent survival, production of steroid hormones and local factors, as well as oocyte maturation in vitro.

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Molecular architecture and functions of the neuronal cytoskeleton

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100157541 ◽

1990 ◽

Vol 48 (3) ◽

pp. 2-3

Author(s):

Nobutaka Hirokawa

Keyword(s):

Major Elements ◽

Molecular Structures ◽

Organelle Transport ◽

Molecular Architecture ◽

Neuronal Morphogenesis ◽

Microtubule Associated Proteins ◽

Associated Proteins ◽

And Function ◽

Small Clusters

In this symposium I will present our studies about the molecular architecture and function of the cytomatrix of the nerve cells. The nerve cell is a highly polarized cell composed of highly branched dendrites, cell body, and a single long axon along the direction of the impulse propagation. Each part of the neuron takes characteristic shapes for which the cytoskeleton provides the framework. The neuronal cytoskeletons play important roles on neuronal morphogenesis, organelle transport and the synaptic transmission. In the axon neurofilaments (NF) form dense arrays, while microtubules (MT) are arranged as small clusters among the NFs. On the other hand, MTs are distributed uniformly, whereas NFs tend to run solitarily or form small fascicles in the dendrites Quick freeze deep etch electron microscopy revealed various kinds of strands among MTs, NFs and membranous organelles (MO). These structures form major elements of the cytomatrix in the neuron. To investigate molecular nature and function of these filaments first we studied molecular structures of microtubule associated proteins (MAP1A, MAP1B, MAP2, MAP2C and tau), and microtubules reconstituted from MAPs and tubulin in vitro. These MAPs were all fibrous molecules with different length and formed arm like projections from the microtubule surface.

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Decision letter for "Human monocytic myeloid‐derived suppressor cells impair B‐cell phenotype and function in vitro"

10.1002/eji.201948240/v2/decision1 ◽

2019 ◽

Keyword(s):

B Cell ◽

Suppressor Cells ◽

Cell Phenotype ◽

Myeloid Derived Suppressor Cells ◽

And Function

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Review for "Human monocytic myeloid‐derived suppressor cells impair B‐cell phenotype and function in vitro"

10.1002/eji.201948240/v1/review1 ◽

2019 ◽

Keyword(s):

B Cell ◽

Suppressor Cells ◽

Cell Phenotype ◽

Myeloid Derived Suppressor Cells ◽

And Function

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Role of the 807 C/T Polymorphism of the α2 Gene in Platelet GP Ia Collagen Receptor Expression and Function

Thrombosis and Haemostasis ◽

10.1055/s-0037-1614605 ◽

1999 ◽

Vol 81 (06) ◽

pp. 951-956 ◽

Cited By ~ 59

Author(s):

J. Corral ◽

R. González-Conejero ◽

J. Rivera ◽

F. Ortuño ◽

P. Aparicio ◽

...

Keyword(s):

Venous Thrombosis ◽

Cell Types ◽

Receptor Expression ◽

Case Control Studies ◽

Platelet Surface ◽

Vitro Analysis ◽

And Function ◽

In Vitro Analysis

SummaryThe variability of the platelet GP Ia/IIa density has been associated with the 807 C/T polymorphism (Phe 224) of the GP Ia gene in American Caucasian population. We have investigated the genotype and allelic frequencies of this polymorphism in Spanish Caucasians. The T allele was found in 35% of the 284 blood donors analyzed. We confirmed in 159 healthy subjects a significant association between the 807 C/T polymorphism and the platelet GP Ia density. The T allele correlated with high number of GP Ia molecules on platelet surface. In addition, we observed a similar association of this polymorphism with the expression of this protein in other blood cell types. The platelet responsiveness to collagen was determined by “in vitro” analysis of the platelet activation and aggregation response. We found no significant differences in these functional platelet parameters according to the 807 C/T genotype. Finally, results from 3 case/control studies involving 302 consecutive patients (101 with coronary heart disease, 104 with cerebrovascular disease and 97 with deep venous thrombosis) determined that the 807 C/T polymorphism of the GP Ia gene does not represent a risk factor for arterial or venous thrombosis.

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