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ACTL6A suppresses p21 expression to enhance the epidermal squamous cell carcinoma phenotype. Shrestha S, Adhikary G, Xu W, Kandasamy S, Eckert RL Epidermal squamous cell carcinoma (SCC) is a common and highly invasive form of cancer. SCC arises due to ultraviolet light exposure and is associated with increased expression of pro-cancer genes and reduced expression of cancer suppressors. Actin-Like Protein 6A (ACTL6A, BAF53a) is an important protein subunit of ... |
STAT Signaling Modifies Ascl1 Chromatin Binding and Limits Neural Regeneration from Muller Glia in Adult Mouse Retina. Jorstad NL, Wilken MS, Todd L, Finkbeiner C, Nakamura P, Radulovich N, Hooper MJ, Chitsazan A, Wilkerson BA, Rieke F, Reh TA Müller glia (MG) serve as sources for retinal regeneration in non-mammalian vertebrates. We find that this process can be induced in mouse MG, after injury, by transgenic expression of the proneural transcription factor Ascl1 and the HDAC inhibitor TSA. However, new neurons are generated only from a subset... |
Heterochromatin protein 1γ deficiency decreases histone H3K27 methylation in mouse neurosphere neuronal genes. Naruse C, Abe K, Yoshihara T, Kato T, Nishiuchi T, Asano M Heterochromatin protein (HP) 1γ, a component of heterochromatin in eukaryotes, is involved in H3K9 methylation. Although HP1γ is expressed strongly in neural tissues and neural stem cells, its functions are unclear. To elucidate the roles of HP1γ, we analyzed HP1γ -deficient (HP1γ KO) m... |
SIRT1/2 orchestrate acquisition of DNA methylation and loss of histone H3 activating marks to prevent premature activation of inflammatory genes in macrophages. Li T, Garcia-Gomez A, Morante-Palacios O, Ciudad L, Özkaramehmet S, Van Dijck E, Rodríguez-Ubreva J, Vaquero A, Ballestar E Sirtuins 1 and 2 (SIRT1/2) are two NAD-dependent deacetylases with major roles in inflammation. In addition to deacetylating histones and other proteins, SIRT1/2-mediated regulation is coupled with other epigenetic enzymes. Here, we investigate the links between SIRT1/2 activity and DNA methylation in macrophage dif... |
Epigenetic remodelling licences adult cholangiocytes for organoid formation and liver regeneration. Aloia L, McKie MA, Vernaz G, Cordero-Espinoza L, Aleksieva N, van den Ameele J, Antonica F, Font-Cunill B, Raven A, Aiese Cigliano R, Belenguer G, Mort RL, Brand AH, Zernicka-Goetz M, Forbes SJ, Miska EA, Huch M Following severe or chronic liver injury, adult ductal cells (cholangiocytes) contribute to regeneration by restoring both hepatocytes and cholangiocytes. We recently showed that ductal cells clonally expand as self-renewing liver organoids that retain their differentiation capacity into both hepatocytes and ductal ... |
RbAp48 Protein Is a Critical Component of GPR158/OCN Signaling and Ameliorates Age-Related Memory Loss. Kosmidis S, Polyzos A, Harvey L, Youssef M, Denny CA, Dranovsky A, Kandel ER Precisely deciphering the molecular mechanisms of age-related memory loss is crucial to create appropriate therapeutic interventions. We have previously shown that the histone-binding protein RbAp48/Rbbp4 is a molecular determinant of Age-Related Memory Loss. By exploring how this protein regulates the genomic lands... |
H3K4me2 and WDR5 enriched chromatin interacting long non-coding RNAs maintain transcriptionally competent chromatin at divergent transcriptional units. Subhash S, Mishra K, Akhade VS, Kanduri M, Mondal T, Kanduri C Recently lncRNAs have been implicated in the sub-compartmentalization of eukaryotic genome via genomic targeting of chromatin remodelers. To explore the function of lncRNAs in the maintenance of active chromatin, we characterized lncRNAs from the chromatin enriched with H3K4me2 and WDR5 using chromatin RNA immunopre... |
Thyroid hormone receptor and ERRα coordinately regulate mitochondrial fission, mitophagy, biogenesis, and function. Singh BK, Sinha RA, Tripathi M, Mendoza A, Ohba K, Sy JAC, Xie SY, Zhou J, Ho JP, Chang CY, Wu Y, Giguère V, Bay BH, Vanacker JM, Ghosh S, Gauthier K, Hollenberg AN, McDonnell DP, Yen PM Thyroid hormone receptor β1 (THRB1) and estrogen-related receptor α (ESRRA; also known as ERRα) both play important roles in mitochondrial activity. To understand their potential interactions, we performed transcriptome and ChIP-seq analyses and found that many genes that were co-regulated by both T... |
Replication-coupled histone H3.1 deposition determines nucleosome composition and heterochromatin dynamics during Arabidopsis seedling development. Benoit M, Simon L, Desset S, Duc C, Cotterell S, Poulet A, Le Goff S, Tatout C, Probst AV Developmental phase transitions are often characterized by changes in the chromatin landscape and heterochromatin reorganization. In Arabidopsis, clustering of repetitive heterochromatic loci into so-called chromocenters is an important determinant of chromosome organization in nuclear space. Here, we investigated t... |
The Transcriptionally Permissive Chromatin State of Embryonic Stem Cells Is Acutely Tuned to Translational Output. Bulut-Karslioglu A, Macrae TA, Oses-Prieto JA, Covarrubias S, Percharde M, Ku G, Diaz A, McManus MT, Burlingame AL, Ramalho-Santos M A permissive chromatin environment coupled to hypertranscription drives the rapid proliferation of embryonic stem cells (ESCs) and peri-implantation embryos. We carried out a genome-wide screen to systematically dissect the regulation of the euchromatic state of ESCs. The results revealed that cellular growth pathwa... |
Oestrogen Receptor-α binds the FOXP3 promoter and modulates regulatory T-cell function in human cervical cancer Adurthi S. et al. Oestrogen controls Foxp3 expression in regulatory T cells (Treg cells) via a mechanism thought to involve oestrogen receptor alpha (ERα), but the molecular basis and functional impact of ERα signalling in Treg cells remain unclear. We report that ERα ligand oestradiol (E2) is significantly increase... |
5-hydroxymethylcytosine accumulation in postmitotic neurons results in functional demethylation of expressed genes Mellén M. et al. 5-hydroxymethylcytosine (5hmC) occurs at maximal levels in postmitotic neurons, where its accumulation is cell-specific and correlated with gene expression. Here we demonstrate that the distribution of 5hmC in CG and non-CG dinucleotides is distinct and that it reflects the binding specificity and genome occupancy o... |
Epigenome profiling and editing of neocortical progenitor cells during development Albert M. et al. The generation of neocortical neurons from neural progenitor cells (NPCs) is primarily controlled by transcription factors binding to DNA in the context of chromatin. To understand the complex layer of regulation that orchestrates different NPC types from the same DNA sequence, epigenome maps with cell type resoluti... |
Vitamin C induces specific demethylation of H3K9me2 in mouse embryonic stem cells via Kdm3a/b Kevin T. Ebata, Kathryn Mesh, Shichong Liu, Misha Bilenky, Alexander Fekete, Michael G. Acker, Martin Hirst, Benjamin A. Garcia and Miguel Ramalho-Santos
Background
Histone methylation patterns regulate gene expression and are highly dynamic during development. The erasure of histone methylation is carried out by histone demethylase enzymes. We had previously shown that vitamin C enhances the activity of Tet enzymes in embryonic stem (ES) cells, leading to DNA... |
A chronic low dose of Δ9-tetrahydrocannabinol (THC) restores cognitive function in old mice Bilkei-Gorzo A. et al. The balance between detrimental, pro-aging, often stochastic processes and counteracting homeostatic mechanisms largely determines the progression of aging. There is substantial evidence suggesting that the endocannabinoid system (ECS) is part of the latter system because it modulates the physiological processes und... |
The Role of Angiotensin Converting Enzyme 1 within the median preoptic nucleus following chronic intermittent hypoxia Faulk K. et al. Sustained hypertension is an important consequence of obstructive sleep apnea. An animal model of the hypoxemia associated with sleep apnea, chronic intermittent hypoxia (CIH), produces increased sympathetic nerve activity (SNA) and sustained increases in blood pressure. Many mechanisms have been implicated in the h... |
Polycomb repressive complex 2 (PRC2) silences genes responsible for neurodegeneration von Schimmelmann M et al. Normal brain function depends on the interaction between highly specialized neurons that operate within anatomically and functionally distinct brain regions. Neuronal specification is driven by transcriptional programs that are established during early neuronal development and remain in place in the adult brain. The... |
MEP50/PRMT5 Reduces Gene Expression by Histone Arginine Methylation and this Is Reversed by PKCδ/p38δ Signaling Saha K et al. Protein kinase C δ (PKCδ) and p38δ are key proteins in a cascade that stimulates keratinocyte differentiation. This cascade activates transcription of involucrin (hINV) and other genes associated with differentiation. Protein arginine methyltransferase 5 (PRMT5) is an arginine methyltransferase tha... |