Retinoblastoma Binding Protein 4 Maintains Cycling Neural Stem Cells and Prevents DNA Damage and Tp53-Dependent Apoptosis in Rb1 Mutant Neural Progenitors Laura E
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A Computational Approach for Defining a Signature of Β-Cell Golgi Stress in Diabetes Mellitus
Page 1 of 781 Diabetes A Computational Approach for Defining a Signature of β-Cell Golgi Stress in Diabetes Mellitus Robert N. Bone1,6,7, Olufunmilola Oyebamiji2, Sayali Talware2, Sharmila Selvaraj2, Preethi Krishnan3,6, Farooq Syed1,6,7, Huanmei Wu2, Carmella Evans-Molina 1,3,4,5,6,7,8* Departments of 1Pediatrics, 3Medicine, 4Anatomy, Cell Biology & Physiology, 5Biochemistry & Molecular Biology, the 6Center for Diabetes & Metabolic Diseases, and the 7Herman B. Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN 46202; 2Department of BioHealth Informatics, Indiana University-Purdue University Indianapolis, Indianapolis, IN, 46202; 8Roudebush VA Medical Center, Indianapolis, IN 46202. *Corresponding Author(s): Carmella Evans-Molina, MD, PhD ([email protected]) Indiana University School of Medicine, 635 Barnhill Drive, MS 2031A, Indianapolis, IN 46202, Telephone: (317) 274-4145, Fax (317) 274-4107 Running Title: Golgi Stress Response in Diabetes Word Count: 4358 Number of Figures: 6 Keywords: Golgi apparatus stress, Islets, β cell, Type 1 diabetes, Type 2 diabetes 1 Diabetes Publish Ahead of Print, published online August 20, 2020 Diabetes Page 2 of 781 ABSTRACT The Golgi apparatus (GA) is an important site of insulin processing and granule maturation, but whether GA organelle dysfunction and GA stress are present in the diabetic β-cell has not been tested. We utilized an informatics-based approach to develop a transcriptional signature of β-cell GA stress using existing RNA sequencing and microarray datasets generated using human islets from donors with diabetes and islets where type 1(T1D) and type 2 diabetes (T2D) had been modeled ex vivo. To narrow our results to GA-specific genes, we applied a filter set of 1,030 genes accepted as GA associated. -
Benefits of Cancerplex
CancerPlexSM is a comprehensive genetic assessment of a patient’s tumor that guides oncologists towards effective treatment options. What is CancerPlex? CancerPlex is a next generation DNA sequencing test for solid SM tumors. The specific coding regions of over 400 known cancer Potential outcomes from CancerPlex genes are simultaneously determined using a small amount of Identification of variants associated with response or resis- DNA extracted from tumor samples, including formalin-fixed, tance to an FDA-approved therapy for the patient’s disease. paraffin-embedded (FFPE) tissue and cell blocks from fine-needle aspirates or effusions. This analysis is performed in a single assay, Identification of variants associated with response or resis- simplifying and streamlining the test ordering process, and eliminat- tance to a therapy associated with another clinical indication. ing time consuming serial testing. Clinically actionable information unique to each patient’s tumor is consolidated into a simple report. Identification of variants associated with a therapy(s) in CancerPlex reveals missense changes, insertions and deletions, clinical development. and previously described rearrangements of ALK, RET, and ROS. Benefits of CancerPlex: CancerPlex genes were selected because of their importance in tumor The average turn-around-time for CancerPlex is under 10 biology. Analyzing more genes increases the chance of discovering business days, dramatically shortening the waiting period for actionable findings that lead to more choices for treatment. Our initial the start of treatment. results indicate that CancerPlex analysis identifies actionable findings up to 20% more frequently than previously published studies. CancerPlex ordering is simple: KEW provides all necessary shipping materials, can facilitate tissue retrieval and return with Since knowledge of tumor biology changes rapidly, CancerPlex pathologists, and manages 3rd party payment for the test. -
Cellular and Molecular Signatures in the Disease Tissue of Early
Cellular and Molecular Signatures in the Disease Tissue of Early Rheumatoid Arthritis Stratify Clinical Response to csDMARD-Therapy and Predict Radiographic Progression Frances Humby1,* Myles Lewis1,* Nandhini Ramamoorthi2, Jason Hackney3, Michael Barnes1, Michele Bombardieri1, Francesca Setiadi2, Stephen Kelly1, Fabiola Bene1, Maria di Cicco1, Sudeh Riahi1, Vidalba Rocher-Ros1, Nora Ng1, Ilias Lazorou1, Rebecca E. Hands1, Desiree van der Heijde4, Robert Landewé5, Annette van der Helm-van Mil4, Alberto Cauli6, Iain B. McInnes7, Christopher D. Buckley8, Ernest Choy9, Peter Taylor10, Michael J. Townsend2 & Costantino Pitzalis1 1Centre for Experimental Medicine and Rheumatology, William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, Charterhouse Square, London EC1M 6BQ, UK. Departments of 2Biomarker Discovery OMNI, 3Bioinformatics and Computational Biology, Genentech Research and Early Development, South San Francisco, California 94080 USA 4Department of Rheumatology, Leiden University Medical Center, The Netherlands 5Department of Clinical Immunology & Rheumatology, Amsterdam Rheumatology & Immunology Center, Amsterdam, The Netherlands 6Rheumatology Unit, Department of Medical Sciences, Policlinico of the University of Cagliari, Cagliari, Italy 7Institute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow G12 8TA, UK 8Rheumatology Research Group, Institute of Inflammation and Ageing (IIA), University of Birmingham, Birmingham B15 2WB, UK 9Institute of -
Intrinsically Disordered Meningioma-1 Stabilizes the BAF Complex to Cause AML
Article Intrinsically disordered Meningioma-1 stabilizes the BAF complex to cause AML Graphical abstract Authors Simone S. Riedel, Congcong Lu, Hongbo M. Xie, ..., Gerd A. Blobel, Benjamin A. Garcia, Kathrin M. Bernt Correspondence [email protected] In brief Meningioma-1 (MN1) translocations result in overexpression of MN1 through enhancer hijacking, or expression of an MN1 fusion protein. MN1 is an intrinsically disordered polyQ protein. MN1 overexpression is sufficient to cause malignant transformation via over- stabilization of the BAF complex at critical enhancers. Highlights d MN1 translocations in AML result in MN1 overexpression due to enhancer hijacking d MN1 interacts with the myeloid progenitor BAF complex d MN1 over-stabilizes the BAF complex at critical enhancers d Overexpression of the polyQ protein MN1 is sufficient to cause AML Riedel et al., 2021, Molecular Cell 81, 1–17 June 3, 2021 ª 2021 Elsevier Inc. https://doi.org/10.1016/j.molcel.2021.04.014 ll Please cite this article in press as: Riedel et al., Intrinsically disordered Meningioma-1 stabilizes the BAF complex to cause AML, Molecular Cell (2021), https://doi.org/10.1016/j.molcel.2021.04.014 ll Article Intrinsically disordered Meningioma-1 stabilizes the BAF complex to cause AML Simone S. Riedel,1 Congcong Lu,2 Hongbo M. Xie,3 Kevin Nestler,1 Marit W. Vermunt,4 Alexandra Lenard,1 Laura Bennett,5 Nancy A. Speck,5 Ichiro Hanamura,6 Julie A. Lessard,7 Gerd A. Blobel,4,8 Benjamin A. Garcia,2 and Kathrin M. Bernt1,8,9,* 1Division of Pediatric Oncology, Children’s Hospital -
DYRK1A Protein Kinase Promotes Quiescence and Senescence Through DREAM Complex Assembly
Downloaded from genesdev.cshlp.org on September 28, 2021 - Published by Cold Spring Harbor Laboratory Press DYRK1A protein kinase promotes quiescence and senescence through DREAM complex assembly Larisa Litovchick,1,2 Laurence A. Florens,3 Selene K. Swanson,3 Michael P. Washburn,3,4 and James A. DeCaprio1,2,5,6 1Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts 02215, USA; 2Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA; 3Stowers Institute for Biomedical Research, Kansas City, Missouri 64110, USA; 4Department of Pathology and Laboratory Medicine, The University of Kansas Medical Center, Kansas City, Kansas 66160, USA; 5Belfer Institute for Applied Cancer Science, Dana-Farber Cancer Institute, Boston, Massachusetts 02215, USA In the absence of growth signals, cells exit the cell cycle and enter into G0 or quiescence. Alternatively, cells enter senescence in response to inappropriate growth signals such as oncogene expression. The molecular mechanisms required for cell cycle exit into quiescence or senescence are poorly understood. The DREAM (DP, RB [retinoblastoma] , E2F, and MuvB) complex represses cell cycle-dependent genes during quiescence. DREAM contains p130, E2F4, DP1, and a stable core complex of five MuvB-like proteins: LIN9, LIN37, LIN52, LIN54, and RBBP4. In mammalian cells, the MuvB core dissociates from p130 upon entry into the cell cycle and binds to BMYB during S phase to activate the transcription of genes expressed late in the cell cycle. We used mass spectroscopic analysis to identify phosphorylation sites that regulate the switch of the MuvB core from BMYB to DREAM. Here we report that DYRK1A can specifically phosphorylate LIN52 on serine residue 28, and that this phosphorylation is required for DREAM assembly. -
1714 Gene Comprehensive Cancer Panel Enriched for Clinically Actionable Genes with Additional Biologically Relevant Genes 400-500X Average Coverage on Tumor
xO GENE PANEL 1714 gene comprehensive cancer panel enriched for clinically actionable genes with additional biologically relevant genes 400-500x average coverage on tumor Genes A-C Genes D-F Genes G-I Genes J-L AATK ATAD2B BTG1 CDH7 CREM DACH1 EPHA1 FES G6PC3 HGF IL18RAP JADE1 LMO1 ABCA1 ATF1 BTG2 CDK1 CRHR1 DACH2 EPHA2 FEV G6PD HIF1A IL1R1 JAK1 LMO2 ABCB1 ATM BTG3 CDK10 CRK DAXX EPHA3 FGF1 GAB1 HIF1AN IL1R2 JAK2 LMO7 ABCB11 ATR BTK CDK11A CRKL DBH EPHA4 FGF10 GAB2 HIST1H1E IL1RAP JAK3 LMTK2 ABCB4 ATRX BTRC CDK11B CRLF2 DCC EPHA5 FGF11 GABPA HIST1H3B IL20RA JARID2 LMTK3 ABCC1 AURKA BUB1 CDK12 CRTC1 DCUN1D1 EPHA6 FGF12 GALNT12 HIST1H4E IL20RB JAZF1 LPHN2 ABCC2 AURKB BUB1B CDK13 CRTC2 DCUN1D2 EPHA7 FGF13 GATA1 HLA-A IL21R JMJD1C LPHN3 ABCG1 AURKC BUB3 CDK14 CRTC3 DDB2 EPHA8 FGF14 GATA2 HLA-B IL22RA1 JMJD4 LPP ABCG2 AXIN1 C11orf30 CDK15 CSF1 DDIT3 EPHB1 FGF16 GATA3 HLF IL22RA2 JMJD6 LRP1B ABI1 AXIN2 CACNA1C CDK16 CSF1R DDR1 EPHB2 FGF17 GATA5 HLTF IL23R JMJD7 LRP5 ABL1 AXL CACNA1S CDK17 CSF2RA DDR2 EPHB3 FGF18 GATA6 HMGA1 IL2RA JMJD8 LRP6 ABL2 B2M CACNB2 CDK18 CSF2RB DDX3X EPHB4 FGF19 GDNF HMGA2 IL2RB JUN LRRK2 ACE BABAM1 CADM2 CDK19 CSF3R DDX5 EPHB6 FGF2 GFI1 HMGCR IL2RG JUNB LSM1 ACSL6 BACH1 CALR CDK2 CSK DDX6 EPOR FGF20 GFI1B HNF1A IL3 JUND LTK ACTA2 BACH2 CAMTA1 CDK20 CSNK1D DEK ERBB2 FGF21 GFRA4 HNF1B IL3RA JUP LYL1 ACTC1 BAG4 CAPRIN2 CDK3 CSNK1E DHFR ERBB3 FGF22 GGCX HNRNPA3 IL4R KAT2A LYN ACVR1 BAI3 CARD10 CDK4 CTCF DHH ERBB4 FGF23 GHR HOXA10 IL5RA KAT2B LZTR1 ACVR1B BAP1 CARD11 CDK5 CTCFL DIAPH1 ERCC1 FGF3 GID4 HOXA11 IL6R KAT5 ACVR2A -
Metastatic Adrenocortical Carcinoma Displays Higher Mutation Rate and Tumor Heterogeneity Than Primary Tumors
ARTICLE DOI: 10.1038/s41467-018-06366-z OPEN Metastatic adrenocortical carcinoma displays higher mutation rate and tumor heterogeneity than primary tumors Sudheer Kumar Gara1, Justin Lack2, Lisa Zhang1, Emerson Harris1, Margaret Cam2 & Electron Kebebew1,3 Adrenocortical cancer (ACC) is a rare cancer with poor prognosis and high mortality due to metastatic disease. All reported genetic alterations have been in primary ACC, and it is 1234567890():,; unknown if there is molecular heterogeneity in ACC. Here, we report the genetic changes associated with metastatic ACC compared to primary ACCs and tumor heterogeneity. We performed whole-exome sequencing of 33 metastatic tumors. The overall mutation rate (per megabase) in metastatic tumors was 2.8-fold higher than primary ACC tumor samples. We found tumor heterogeneity among different metastatic sites in ACC and discovered recurrent mutations in several novel genes. We observed 37–57% overlap in genes that are mutated among different metastatic sites within the same patient. We also identified new therapeutic targets in recurrent and metastatic ACC not previously described in primary ACCs. 1 Endocrine Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. 2 Center for Cancer Research, Collaborative Bioinformatics Resource, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. 3 Department of Surgery and Stanford Cancer Institute, Stanford University, Stanford, CA 94305, USA. Correspondence and requests for materials should be addressed to E.K. (email: [email protected]) NATURE COMMUNICATIONS | (2018) 9:4172 | DOI: 10.1038/s41467-018-06366-z | www.nature.com/naturecommunications 1 ARTICLE NATURE COMMUNICATIONS | DOI: 10.1038/s41467-018-06366-z drenocortical carcinoma (ACC) is a rare malignancy with types including primary ACC from the TCGA to understand our A0.7–2 cases per million per year1,2. -
Genetic Variants in A
Neurobiology of Aging 35 (2014) 2881.e7e2881.e10 Contents lists available at ScienceDirect Neurobiology of Aging journal homepage: www.elsevier.com/locate/neuaging Brief communication Genetic variants in a ‘cAMP element binding protein’ (CREB)-dependent histone acetylation pathway influence memory performance in cognitively healthy elderly individuals Sandra Barral a,b, Christiane Reitz a,b, Scott A. Small a,b, Richard Mayeux a,b,* a Department of Neurology, Columbia University Medical Center, New York, NY, USA b Taub Institute for Research on Alzheimer’s Disease and the Aging Brain, Columbia University, New York, NY, USA article info abstract Article history: The molecular pathways underlying age-related memory changes remain unclear. There is a substantial Received 5 March 2014 genetic contribution to memory performance through life span. A recent study has implicated RbAp48, Received in revised form 17 June 2014 which mediates its effect on age-related memory decline by interacting with cyclic adenosine mono- Accepted 24 June 2014 phosphate responsive element binding protein (CREB)1 binding protein and influencing this histone Available online 28 June 2014 acetylation pathway. To validate these findings, we tested whether genetic variants in RbAp48, CREB1, and CREBBP are associated with memory performance in 3 independent data sets consisting of 2674 Keywords: cognitively healthy elderly individuals. Genetic variant rs2526690 in the CREBBP gene was significantly Histone metabolism ¼ Â À4 Meta-analysis associated with episodic memory performance (pmeta 3.7 10 ) in a multivariate model adjusted for Episodic memory performance age, sex, and apolipoprotein E status. Identifying genetic variants that modulate mechanisms of cognitive aging will allow identifying valid targets for therapeutic intervention. -
Engaging Chromatin: PRC2 Structure Meets Function
www.nature.com/bjc REVIEW ARTICLE Engaging chromatin: PRC2 structure meets function Paul Chammas1, Ivano Mocavini1 and Luciano Di Croce1,2,3 Polycomb repressive complex 2 (PRC2) is a key epigenetic multiprotein complex involved in the regulation of gene expression in metazoans. PRC2 is formed by a tetrameric core that endows the complex with histone methyltransferase activity, allowing it to mono-, di- and tri-methylate histone H3 on lysine 27 (H3K27me1/2/3); H3K27me3 is a hallmark of facultative heterochromatin. The core complex of PRC2 is bound by several associated factors that are responsible for modulating its targeting specificity and enzymatic activity. Depletion and/or mutation of the subunits of this complex can result in severe developmental defects, or even lethality. Furthermore, mutations of these proteins in somatic cells can be drivers of tumorigenesis, by altering the transcriptional regulation of key tumour suppressors or oncogenes. In this review, we present the latest results from structural studies that have characterised PRC2 composition and function. We compare this information with data and literature for both gain-of function and loss-of-function missense mutations in cancers to provide an overview of the impact of these mutations on PRC2 activity. British Journal of Cancer (2020) 122:315–328; https://doi.org/10.1038/s41416-019-0615-2 BACKGROUND and embryonic ectoderm development (EED) (Table 1). These Transcriptional diversity is one of the hallmarks of cellular three proteins form the minimal core that confers histone identity. It is largely regulated at the level of chromatin, where methyltransferase (HMT) activity. A fourth factor, retinoblastoma- different protein complexes act as initiators, enhancers and/or binding protein (RBBP)4/7 (also known as RBAP48/46), has a repressors of transcription. -
SUPPLEMENTARY NOTE Co-Activation of GR and NFKB
SUPPLEMENTARY NOTE Co-activation of GR and NFKB alters the repertoire of their binding sites and target genes. Nagesha A.S. Rao1*, Melysia T. McCalman1,*, Panagiotis Moulos2,4, Kees-Jan Francoijs1, 2 2 3 3,5 Aristotelis Chatziioannou , Fragiskos N. Kolisis , Michael N. Alexis , Dimitra J. Mitsiou and 1,5 Hendrik G. Stunnenberg 1Department of Molecular Biology, Radboud University Nijmegen, the Netherlands 2Metabolic Engineering and Bioinformatics Group, Institute of Biological Research and Biotechnology, National Hellenic Research Foundation, Athens, Greece 3Molecular Endocrinology Programme, Institute of Biological Research and Biotechnology, National Hellenic Research Foundation, Greece 4These authors contributed equally to this work 5 Corresponding authors E-MAIL: [email protected] ; TEL: +31-24-3610524; FAX: +31-24-3610520 E-MAIL: [email protected] ; TEL: +30-210-7273741; FAX: +30-210-7273677 Running title: Global GR and NFKB crosstalk Keywords: GR, p65, genome-wide, binding sites, crosstalk SUPPLEMENTARY FIGURES/FIGURE LEGENDS AND SUPPLEMENTARY TABLES 1 Rao118042_Supplementary Fig. 1 A Primary transcript Mature mRNA TNF/DMSO TNF/DMSO 8 12 r=0.74, p< 0.001 r=0.61, p< 0.001 ) 2 ) 10 2 6 8 4 6 4 2 2 0 Fold change (mRNA) (log Fold change (primRNA) (log 0 −2 −2 −2 0 2 4 −2 0 2 4 Fold change (RNAPII) (log2) Fold change (RNAPII) (log2) B chr5: chrX: 56 _ 104 _ DMSO DMSO 1 _ 1 _ 56 _ 104 _ TA TA 1 _ 1 _ 56 _ 104 _ TNF TNF Cluster 1 1 _ Cluster 2 1 _ 56 _ 104 _ TA+TNF TA+TNF 1 _ 1 _ CCNB1 TSC22D3 chr20: chr17: 25 _ 33 _ DMSO DMSO 1 _ 1 _ 25 _ 33 _ TA TA 1 _ 1 _ 25 _ 33 _ TNF TNF Cluster 3 1 _ Cluster 4 1 _ 25 _ 33 _ TA+TNF TA+TNF 1 _ 1 _ GPCPD1 CCL2 chr6: chr22: 77 _ 35 _ DMSO DMSO 1 _ 77 _ 1 _ 35 _ TA TA 1 _ 1 _ 77 _ 35 _ TNF Cluster 5 Cluster 6 TNF 1 _ 1 _ 77 _ 35 _ TA+TNF TA+TNF 1 _ 1 _ TNFAIP3 DGCR6 2 Supplementary Figure 1. -
RBBP4 Protein Full-Length Recombinant Human Protein Expressed in Sf9 Cells
Catalog # Aliquot Size R314-30G-20 20 µg R314-30G-50 50 µg RBBP4 Protein Full-length recombinant human protein expressed in Sf9 cells Catalog # R314-30G Lot # U1595-3 Product Description Purity Full-length recombinant human RBBP4 was expressed by baculovirus in Sf9 insect cells using an N-terminal GST tag. The gene accession number is BC075836. The purity of RBBP4 was determined Gene Aliases to be >90% by densitometry. Approx. MW 75 kDa. NURF55, RBAP48 Formulation Recombinant protein stored in 50mM Tris-HCl, pH 7.5, 150mM NaCl, 10mM glutathione, 0.1mM EDTA, 0.25mM DTT, 0.1mM PMSF, 25% glycerol. Storage and Stability Store product at –70oC. For optimal storage, aliquot target into smaller quantities after centrifugation and store at recommended temperature. For most favorable performance, avoid repeated handling and multiple freeze/thaw cycles. Scientific Background Histone-binding protein RBBP4 (RBBP4) was initially identified as one of the strongest interactions when a CREB-CREB binding protein (CBP) complex was used as bait to screen a mouse embryo cDNA library in yeast. May target chromatin assembly factors, chromatin remodeling factors and histone deacetylases to their RBBP4 Protein histone substrates in a manner that is regulated by Full-length recombinant human protein expressed in Sf9 cells nucleosomal DNA. Catalog # R314-30G References Lot # U1595-3 Purity >90% Concentration 0.1 µg/µl 1. Zhang Q, et al: Histone binding protein RbAp48 interacts Stability 1yr at –70oC from date of shipment with a complex of CREB binding protein and phospho- Storage & Shipping Store product at –70oC. For optimal rylated CREB. -
PWWP2A Binds Distinct Chromatin Moieties and Interacts with an MTA1-Specific Core Nurd Complex
ARTICLE DOI: 10.1038/s41467-018-06665-5 OPEN PWWP2A binds distinct chromatin moieties and interacts with an MTA1-specific core NuRD complex Stephanie Link1,2, Ramona M.M. Spitzer1,2, Maryam Sana3, Mario Torrado3, Moritz C. Völker-Albert1, Eva C. Keilhauer4,9, Thomas Burgold5,10, Sebastian Pünzeler1,11, Jason K.K. Low3, Ida Lindström 3, Andrea Nist6, Catherine Regnard1, Thorsten Stiewe 6,7, Brian Hendrich5, Axel Imhof 1,8, Matthias Mann 4,8, Joel P. Mackay 3, Marek Bartkuhn2 & Sandra B. Hake 2,8 1234567890():,; Chromatin structure and function is regulated by reader proteins recognizing histone mod- ifications and/or histone variants. We recently identified that PWWP2A tightly binds to H2A. Z-containing nucleosomes and is involved in mitotic progression and cranial–facial devel- opment. Here, using in vitro assays, we show that distinct domains of PWWP2A mediate binding to free linker DNA as well as H3K36me3 nucleosomes. In vivo, PWWP2A strongly recognizes H2A.Z-containing regulatory regions and weakly binds H3K36me3-containing gene bodies. Further, PWWP2A binds to an MTA1-specific subcomplex of the NuRD complex (M1HR), which consists solely of MTA1, HDAC1, and RBBP4/7, and excludes CHD, GATAD2 and MBD proteins. Depletion of PWWP2A leads to an increase of acetylation levels on H3K27 as well as H2A.Z, presumably by impaired chromatin recruitment of M1HR. Thus, this study identifies PWWP2A as a complex chromatin-binding protein that serves to direct the deacetylase complex M1HR to H2A.Z-containing chromatin, thereby promoting changes in histone acetylation levels. 1 Department of Molecular Biology, BioMedical Center (BMC), Ludwig-Maximilians-University Munich, 82152 Planegg-Martinsried, Germany.