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Cornelia G Spruijt, Martijn S Luijsterburg, Roberta Menafra, Rik G H Lindeboom, Pascal W T C Jansen, Raghu Ram Edupuganti, Marijke P Baltissen, Wouter W Wiegant, Moritz C Voelker-Albert, Filomena Matarese, Anneloes Mensinga, Ina Poser, Harmjan R Vos, Hendrik G Stunnenberg, Haico van Attikum, Michiel Vermeulen
NuRD (nucleosome remodeling and histone deacetylase) is a versatile multi-protein complex with roles in transcription regulation and the DNA damage response. Here, we show that ZMYND8 bridges NuRD to a number of putative DNA-binding zinc finger proteins. The MYND domain of ZMYND8 directly interacts with PPPLΦ motifs in the NuRD subunit GATAD2A. Both GATAD2A and GATAD2B exclusively form homodimers and define mutually exclusive NuRD subcomplexes. ZMYND8 and NuRD share a large number of genome-wide binding sites, mostly active promoters and enhancers...
October 11, 2016: Cell Reports
Ke He, Hu Qu, Hui Wang, Shun Zhang, Xin-Hong Qian, Wei Li
Metastasis-associated protein 3 (MTA3) is a subunit of the Mi-2/nucleosome remodeling and deacetylase (NuRD) protein complex, with relevant roles in the regulation of cancerous epithelial to mesenchymal transition (ETM) in an estrogen-dependent manner, recently involved in the modulation of different physiological processes. Although these findings connect MTA3 expression with hormonal signaling in various systems, little is known about whether this relationship is conserved in testis where hormonal action is intensive...
September 27, 2016: Endocrinology
Joanna Bednarczyk, Konrad J Dębski, Anna M Bot, Katarzyna Lukasiuk
The aim of the present study was to examine involvement of MBD3 (methyl-CpG-binding domain protein 3), a protein involved in reading DNA methylation patterns, in epileptogenesis and epilepsy. We used a well-characterized rat model of temporal lobe epilepsy that is triggered by status epilepticus, evoked by electrical stimulation of the amygdala. Stimulated and sham-operated animals were sacrificed 14 days after stimulation. We found that MBD3 transcript was present in neurons, oligodendrocytes, and astrocytes in both control and epileptic animals...
2016: Scientific Reports
Arezu Jahani-Asl, Cheng Cheng, Chi Zhang, Azad Bonni
Intellectual disability encompasses a large set of neurodevelopmental disorders of cognition that are more common in males than females. Although mutations in over 100 X-linked genes associated to intellectual disability have been identified, only a few X-linked intellectual disability proteins have been intensively studied. Hence, the molecular mechanisms underlying the majority of X-linked intellectual disability disorders remain poorly understood. A substantial fraction of X-linked intellectual disability genes encode nuclear proteins, suggesting that elucidating their functions in the regulation of transcription may provide novel insights into the pathogenesis of intellectual disability...
September 12, 2016: Neurobiology of Disease
Constanza Vásquez-Doorman, Christian P Petersen
Regeneration involves precise control of cell fate to produce an appropriate complement of tissues formed within a blastema. Several chromatin-modifying complexes have been identified as required for regeneration in planarians, but it is unclear whether this class of molecules uniformly promotes the production of differentiated cells. We identify a function for p66, encoding a DNA-binding protein component of the NuRD (nucleosome remodeling and deacetylase) complex, as well as the chromodomain helicase chd4, in suppressing production of photoreceptor neurons (PRNs) in planarians...
June 2016: Regeneration
Zi-Jun Gao, Jie Min, Xu-Cai Wu, Tian Yang, Chang-You Yan, Bu-Huai Dong, Tao Zhang
The Metastasis-associated protein 1 (MTA1) coregulator, an essential component of the nucleosome remodeling and deacetylase (NuRD) complex, potentiates neuroprotective effects against ischemia/reperfusion (I/R) injury. But the underlying mechanism(s) remain largely unknown. Here, we discovered that neuronal MTA1 was a target of oxidative stress, and stimulation of neurons with oxygen glucose deprivation (OGD) treatment significantly inhibited MTA1 expression. Additionally, MTA1 depletion augmented ischemic oxidative stress and thus promoted oxidative stress-induced neuronal cell death by OGD...
October 7, 2016: Biochemical and Biophysical Research Communications
Hsiang-Chieh Lee, Osman Oguz Ahsen, Kaicheng Liang, Zhao Wang, Cody Cleveland, Lucas Booth, Benjamin Potsaid, Vijaysekhar Jayaraman, Alex E Cable, Hiroshi Mashimo, Robert Langer, Giovanni Traverso, James G Fujimoto
We demonstrate a micromotor balloon imaging catheter for ultrahigh speed endoscopic optical coherence tomography (OCT) which provides wide area, circumferential structural and angiographic imaging of the esophagus without contrast agents. Using a 1310 nm MEMS tunable wavelength swept VCSEL light source, the system has a 1.2 MHz A-scan rate and ~8.5 µm axial resolution in tissue. The micromotor balloon catheter enables circumferential imaging of the esophagus at 240 frames per second (fps) with a ~30 µm (FWHM) spot size...
August 1, 2016: Biomedical Optics Express
Y Xu, L Qin, T Sun, H Wu, T He, Z Yang, Q Mo, L Liao, J Xu
The heterogeneous breast cancers can be classified into different subtypes according to their histopathological characteristics and molecular signatures. Foxa1 expression is linked with luminal breast cancer (LBC) with good prognosis, whereas Twist1 expression is associated with basal-like breast cancer (BLBC) with poor prognosis owing to its role in promoting epithelial-to-mesenchymal transition (EMT), invasiveness and metastasis. However, the regulatory and functional relationships between Twist1 and Foxa1 in breast cancer progression are unknown...
August 15, 2016: Oncogene
Gabrielle Gay, Laurence Braun, Marie-Pierre Brenier-Pinchart, Julien Vollaire, Véronique Josserand, Rose-Laurence Bertini, Aurélie Varesano, Bastien Touquet, Pieter-Jan De Bock, Yohann Coute, Isabelle Tardieux, Alexandre Bougdour, Mohamed-Ali Hakimi
An early hallmark of Toxoplasma gondii infection is the rapid control of the parasite population by a potent multifaceted innate immune response that engages resident and homing immune cells along with pro- and counter-inflammatory cytokines. In this context, IFN-γ activates a variety of T. gondii-targeting activities in immune and nonimmune cells but can also contribute to host immune pathology. T. gondii has evolved mechanisms to timely counteract the host IFN-γ defenses by interfering with the transcription of IFN-γ-stimulated genes...
August 22, 2016: Journal of Experimental Medicine
(no author information available yet)
In this issue, we highlight a report by Hiraoka et al. that provides insight into the signalling pathways that regulate the transition from meiotic prophase I to metaphase I; work by Franco et al. that shows how communication between clonal cancer cells promotes tumour growth; and a study by Zhang, Aubert et al. that identifies a core NuRD chromatin remodelling complex.
August 2016: FEBS Journal
Anzy Miller, Meryem Ralser, Susan L Kloet, Remco Loos, Ryuichi Nishinakamura, Paul Bertone, Michiel Vermeulen, Brian Hendrich
Sall4 is an essential transcription factor for early mammalian development and is frequently overexpressed in cancer. Although it is reported to play an important role in embryonic stem cell (ESC) self-renewal, whether it is an essential pluripotency factor has been disputed. Here, we show that Sall4 is dispensable for mouse ESC pluripotency. Sall4 is an enhancer-binding protein that prevents precocious activation of the neural gene expression programme in ESCs but is not required for maintenance of the pluripotency gene regulatory network...
September 1, 2016: Development
Yue Yang, Tomoko Yamada, Kelly K Hill, Martin Hemberg, Naveen C Reddy, Ha Y Cho, Arden N Guthrie, Anna Oldenborg, Shane A Heiney, Shogo Ohmae, Javier F Medina, Timothy E Holy, Azad Bonni
Activity-dependent transcription influences neuronal connectivity, but the roles and mechanisms of inactivation of activity-dependent genes have remained poorly understood. Genome-wide analyses in the mouse cerebellum revealed that the nucleosome remodeling and deacetylase (NuRD) complex deposits the histone variant H2A.z at promoters of activity-dependent genes, thereby triggering their inactivation. Purification of translating messenger RNAs from synchronously developing granule neurons (Sync-TRAP) showed that conditional knockout of the core NuRD subunit Chd4 impairs inactivation of activity-dependent genes when neurons undergo dendrite pruning...
July 15, 2016: Science
Philipp Olias, Ronald D Etheridge, Yong Zhang, Michael J Holtzman, L David Sibley
Interferon gamma (IFN-γ) is an essential mediator of host defense against intracellular pathogens, including the protozoan parasite Toxoplasma gondii. However, prior T. gondii infection blocks IFN-γ-dependent gene transcription, despite the downstream transcriptional activator STAT1 being activated and bound to cognate nuclear promoters. We identify the parasite effector that blocks STAT1-dependent transcription and show it is associated with recruitment of the Mi-2 nucleosome remodeling and deacetylase (NuRD) complex, a chromatin-modifying repressor...
July 13, 2016: Cell Host & Microbe
Tianyi Zhang, Zhentao Sheng, Wei Du
Inactivation of HDAC1 and its homolog HDAC2 or addition of HDAC inhibitors in mammalian systems induces apoptosis, cell cycle arrest, and developmental defects. Although these phenotypes have been extensively characterized, the precise underlying mechanisms remain unclear, particularly in in vivo settings. In this study, we show that inactivation of Rpd3, the only HDAC1 and HDAC2 ortholog in Drosophila, induced apoptosis and clone elimination in the developing eye and wing imaginal discs. Depletion of Rpd3 by RNAi cell-autonomously increased JNK activities and decreased activities of Yki, the nuclear effecter of Hippo signaling pathway...
August 2016: Mechanisms of Development
Elenoe C Smith, Stuart H Orkin
The β-hemoglobinopathies are inherited disorders resulting from altered coding potential or expression of the adult β-globin gene. Impaired expression of β-globin reduces adult hemoglobin (HbA, α2β2) production, the hallmark of β-thalassemia. A single base mutation at codon 6 leads to formation of HbS (α2β(S) 2) and sickle cell disease. While the basis of these diseases is known, therapy remains largely supportive. Bone marrow transplantation is the only curative therapy. Patients with elevated levels of fetal hemoglobin (HbF, α2γ2) as adults exhibit reduced symptoms and enhanced survival...
June 23, 2016: Human Molecular Genetics
Kathleen H Wood, Zhaolan Zhou
DNA methylation is an epigenetic mark that is essential for many biological processes and is linked to diseases such as cancer. Methylation is usually associated with transcriptional silencing, but new research has challenged this model. Both transcriptional activation and repression have recently been found to be associated with DNA methylation in a context-specific manner. How DNA methylation patterns are interpreted into different functional output remains poorly understood. One mechanism involves the protein 'readers' of methylation, which includes the methyl-CpG binding domain (MBD) family of proteins...
2016: Frontiers in Genetics
Lai Man Natalie Wu, Jincheng Wang, Andrea Conidi, Chuntao Zhao, Haibo Wang, Zachary Ford, Liguo Zhang, Christiane Zweier, Brian G Ayee, Patrice Maurel, An Zwijsen, Jonah R Chan, Michael P Jankowski, Danny Huylebroeck, Q Richard Lu
The mechanisms that coordinate and balance a complex network of opposing regulators to control Schwann cell (SC) differentiation remain elusive. Here we demonstrate that zinc-finger E-box-binding homeobox 2 (Zeb2, also called Sip1) transcription factor is a critical intrinsic timer that controls the onset of SC differentiation by recruiting histone deacetylases HDAC 1 and 2 (HDAC1/2) and nucleosome remodeling and deacetylase complex (NuRD) co-repressor complexes in mice. Zeb2 deletion arrests SCs at an undifferentiated state during peripheral nerve development and inhibits remyelination after injury...
August 2016: Nature Neuroscience
Rosa Morra, Tomas Fessl, Yuchong Wang, Erika J Mancini, Roman Tuma
Chromatin-remodeling ATPases modulate histones-DNA interactions within nucleosomes and regulate transcription. At the heart of remodeling, ATPase is a helicase-like motor flanked by a variety of conserved targeting domains. CHD4 is the core subunit of the nucleosome remodeling and deacetylase complex NuRD and harbors tandem plant homeo finger (tPHD) and chromo (tCHD) domains. We describe a multifaceted approach to link the domain structure with function, using quantitative assays for DNA and histone binding, ATPase activity, shape reconstruction from solution scattering data, and single molecule translocation assays...
2016: Methods in Molecular Biology
Z Liu, N Lam, E Wang, R A Virden, B Pawel, E F Attiyeh, J M Maris, C J Thiele
As a transcription factor, localization to the nucleus and the recruitment of cofactors to regulate gene transcription is essential. Nuclear localization and nucleosome remodeling and histone deacetylase (NuRD) complex binding are required for the zinc-finger transcription factor CASZ1 to function as a neuroblastoma (NB) tumor suppressor. However, the critical amino acids (AAs) that are required for CASZ1 interaction with NuRD complex and the regulation of CASZ1 subcellular localization have not been characterized...
June 6, 2016: Oncogene
Zhongliang Zhao, Marcel A Dammert, Sven Hoppe, Holger Bierhoff, Ingrid Grummt
Attenuation of ribosome biogenesis in suboptimal growth environments is crucial for cellular homeostasis and genetic integrity. Here, we show that shutdown of rRNA synthesis in response to elevated temperature is brought about by mechanisms that target both the RNA polymerase I (Pol I) transcription machinery and the epigenetic signature of the rDNA promoter. Upon heat shock, the basal transcription factor TIF-IA is inactivated by inhibition of CK2-dependent phosphorylations at Ser170/172. Attenuation of pre-rRNA synthesis in response to heat stress is accompanied by upregulation of PAPAS, a long non-coding RNA (lncRNA) that is transcribed in antisense orientation to pre-rRNA...
September 30, 2016: Nucleic Acids Research
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