ThPOK represses CXXC5, which induces methylation of histone H3 lysine 9 in Cd40lg promoter by association with SUV39H1: implications in repression of CD40L expression in CD8+ cytotoxic T cells.
Journal of Leukocyte Biology 100(2):327 (2016)
CD40 ligand is induced in CD4(+) Th cells upon TCR stimulation and provides an activating signal to B cells, making CD40 ligand an important molecule for Th cell function. However, the detailed molecular mechanisms, whereby CD40 ligand becomes expressed on the cell surface in T cells remain uncl...
Functional analysis of AEBP2, a PRC2 Polycomb protein, reveals a Trithorax phenotype in embryonic development and in ESCs.
Development 143(15):2716 (2016)
The Polycomb repressive complexes PRC1 and PRC2 are key mediators of heritable gene silencing in multicellular organisms. Here, we characterise AEBP2, a known PRC2 co-factor which, in vitro, has been shown to stimulate PRC2 activity. We show that AEBP2 localises specifically to PRC2 target loci,...
Activation of Endogenous Retroviruses in Dnmt1(-/-) ESCs Involves Disruption of SETDB1-Mediated Repression by NP95 Binding to Hemimethylated DNA.
Cell Stem Cell 19(1):81 (2016)
Repression of endogenous retroviruses (ERVs) in mammals involves several epigenetic mechanisms. Acute loss of the maintenance methyltransferase Dnmt1 induces widespread DNA demethylation and transcriptional activation of ERVs, including CpG-rich IAP (intracisternal A particle) proviruses. Here, ...
Immunoresponsive Gene 1 and Itaconate Inhibit Succinate Dehydrogenase to Modulate Intracellular Succinate Levels.
Journal of Biological Chemistry 291(27):14274 (2016)
Metabolic reprogramming is emerging as a hallmark of the innate immune response, and the dynamic control of metabolites such as succinate serves to facilitate the execution of inflammatory responses in macrophages and other immune cells. Immunoresponsive gene 1 (Irg1) expression is induced by in...
Hyperactivation of JAK1 tyrosine kinase induces stepwise, progressive pruritic dermatitis.
Journal of Clinical Investigation 126(6):2064 (2016)
Skin homeostasis is maintained by the continuous proliferation and differentiation of epidermal cells. The skin forms a strong but flexible barrier against microorganisms as well as physical and chemical insults; however, the physiological mechanisms that maintain this barrier are not fully unde...
Genetic defects in a His-Purkinje system transcription factor, IRX3, cause lethal cardiac arrhythmias.
European Heart Journal 37(18):1469 (2016)
Ventricular fibrillation (VF), the main cause of sudden cardiac death (SCD), occurs most frequently in the acute phase of myocardial infarction: a certain fraction of VF, however, develops in an apparently healthy heart, referred as idiopathic VF. The contribution of perturbation in the fast con...
Role of Polycomb RYBP in Maintaining the B-1-to-B-2 B-Cell Lineage Switch in Adult Hematopoiesis.
Molecular and Cellular Biology 36(6):900 (2016)
Polycomb chromatin modifiers regulate hematopoietic pluripotent stem and progenitor cell self-renewal and expansion. Polycomb complex redundancy and biochemical heterogeneity complicate the unraveling of the functional contributions of distinct components. We have studied the hematopoietic activ...
De novo DNA methylation drives 5hmC accumulation in mouse zygotes.
Nature Cell Biology 18(2):225 (2016)
Zygotic epigenetic reprogramming entails genome-wide DNA demethylation that is accompanied by Tet methylcytosine dioxygenase 3 (Tet3)-driven oxidation of 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC; refs 1-4). Here we demonstrate using detailed immunofluorescence analysis and ultrase...
RING1 proteins contribute to early proximal-distal specification of the forelimb bud by restricting Meis2 expression.
Development 143(2):276 (2016)
Polycomb group (PcG) proteins play a pivotal role in silencing developmental genes and help to maintain various stem and precursor cells and regulate their differentiation. PcG factors also regulate dynamic and complex regional specification, particularly in mammals, but this activity is mechani...
Polycomb Complex PRC1 Preserves Intestinal Stem Cell Identity by Sustaining Wnt/β-Catenin Transcriptional Activity.
Cell Stem Cell 18(1):91 (2016)
Polycomb repressive complexes (PRCs) are among the most important gatekeepers of establishing and maintaining cell identity in metazoans. PRC1, which plays a dominant role in this context, executes its functions via multiple subcomplexes, which all contribute to H2AK119 mono-ubiquitination (H2Au...
Polycomb in Transcriptional Phase Transition of Developmental Genes.
Trends in Biochemical Sciences 41(1):9 (2016)
Combinatorial associations between distinct chromatin domains, namely promoters and cis-regulatory elements, determine transcriptional status. Developmental regulatory gene expression, mostly regulated by the Polycomb/Trithorax group of chromatin regulators, is often temporally and spatially spe...
Generation of Novel Traj18-Deficient Mice Lacking Vα14 Natural Killer T Cells with an Undisturbed T Cell Receptor α-Chain Repertoire.
PLoS ONE 11(4):e0153347 (2016)
Invariant Vα14 natural killer T (NKT) cells, characterized by the expression of a single invariant T cell receptor (TCR) α chain encoded by rearranged Trav11 (Vα14)-Traj18 (Jα18) gene segments in mice, and TRAV10 (Vα24)-TRAJ18 (Jα18) in humans, mediate adjuvant effects to activate various effect...
Requirement of Stat3 Signaling in the Postnatal Development of Thymic Medullary Epithelial Cells.
PLoS Genetics 12(1):e1005776 (2016)
Thymic medullary regions are formed in neonatal mice as islet-like structures, which increase in size over time and eventually fuse a few weeks after birth into a continuous structure. The development of medullary thymic epithelial cells (TEC) is dependent on NF-κB associated signaling though ot...
Loss of Pcgf5 Affects Global H2A Monoubiquitination but Not the Function of Hematopoietic Stem and Progenitor Cells.
PLoS ONE 11(5):e0154561 (2016)
Polycomb-group RING finger proteins (Pcgf1-Pcgf6) are components of Polycomb repressive complex 1 (PRC1)-related complexes that catalyze monoubiquitination of histone H2A at lysine 119 (H2AK119ub1), an epigenetic mark associated with repression of genes. Pcgf5 has been characterized as a compone...
Polycomb repressive complex PRC1 spatially constrains the mouse embryonic stem cell genome.
Nature Genetics 47(10):1179 (2015)
The Polycomb repressive complexes PRC1 and PRC2 maintain embryonic stem cell (ESC) pluripotency by silencing lineage-specifying developmental regulator genes. Emerging evidence suggests that Polycomb complexes act through controlling spatial genome organization. We show that PRC1 functions as a ...
Roles of histone H3K27 trimethylase Ezh2 in retinal proliferation and differentiation.
Developmental Neurobiology 75(9):947 (2015)
The histone modification H3K27me3 regulates transcription negatively, and Jmjd3 and Ezh2 demethylate and methylate H3K27me3 and H3K27, respectively. We demonstrated previously that Jmjd3 plays pivotal roles in the differentiation of subsets of bipolar (BP) cells by regulating H3K27me3 levels at ...
CNOT3 contributes to early B cell development by controlling Igh rearrangement and p53 mRNA stability.
Journal of Experimental Medicine 212(9):1465 (2015)
The CCR4-NOT deadenylase complex plays crucial roles in mRNA decay and translational repression induced by poly(A) tail shortening. Although the in vitro activities of each component of this complex have been well characterized, its in vivo role in immune cells remains unclear. Here we show that...
Physical interaction between MPP8 and PRC1 complex and its implication for regulation of spermatogenesis.
Biochemical and Biophysical Research Communicat... 458(3):470 (2015)
Epigenetic modifications such as DNA methylation and histone H3 lysine 27 methylation (H3K27me) are repressive marks that silence gene expression. The M phase phosphoprotein (MPP8) associates with proteins involved in both DNA methylation and histone modifications, and therefore, is a potential ...
Generating a transgenic mouse line stably expressing human MHC surface antigen from a HAC carrying multiple genomic BACs.
Chromosoma 124(1):107 (2015)
The human artificial chromosome (HAC) vector is a promising tool to improve the problematic suppression and position effects of transgene expression frequently seen in transgenic cells and animals produced by conventional plasmid or viral vectors. We generated transgenic mice maintaining a singl...
Transcribed enhancers lead waves of coordinated transcription in transitioning mammalian cells.
Science 347(6225):1010 (2015)
Although it is generally accepted that cellular differentiation requires changes to transcriptional networks, dynamic regulation of promoters and enhancers at specific sets of genes has not been previously studied en masse. Exploiting the fact that active promoters and enhancers are transcribed,...