Your browser doesn't support javascript.
loading
Genome-wide programmable transcriptional memory by CRISPR-based epigenome editing.
Nuñez, James K; Chen, Jin; Pommier, Greg C; Cogan, J Zachery; Replogle, Joseph M; Adriaens, Carmen; Ramadoss, Gokul N; Shi, Quanming; Hung, King L; Samelson, Avi J; Pogson, Angela N; Kim, James Y S; Chung, Amanda; Leonetti, Manuel D; Chang, Howard Y; Kampmann, Martin; Bernstein, Bradley E; Hovestadt, Volker; Gilbert, Luke A; Weissman, Jonathan S.
Affiliation
  • Nuñez JK; Department of Cellular and Molecular Pharmacology, University of California, San Francisco, CA 94158, USA; Howard Hughes Medical Institute, University of California, San Francisco, CA 94158, USA.
  • Chen J; Department of Cellular and Molecular Pharmacology, University of California, San Francisco, CA 94158, USA; Howard Hughes Medical Institute, University of California, San Francisco, CA 94158, USA.
  • Pommier GC; Department of Urology, University of California, San Francisco, CA 94158, USA; Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, CA 94158, USA.
  • Cogan JZ; Department of Cellular and Molecular Pharmacology, University of California, San Francisco, CA 94158, USA; Howard Hughes Medical Institute, University of California, San Francisco, CA 94158, USA; Tetrad Graduate Program, University of California, San Francisco, CA 94158, USA.
  • Replogle JM; Department of Cellular and Molecular Pharmacology, University of California, San Francisco, CA 94158, USA; Tetrad Graduate Program, University of California, San Francisco, CA 94158, USA; Medical Scientist Training Program, University of California, San Francisco, CA 94158, USA; Whitehead Institute
  • Adriaens C; Department of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02139, USA; Center for Cancer Research, Massachusetts General Hospital, Boston, MA 02129, USA.
  • Ramadoss GN; Institute for Neurodegenerative Diseases, University of California, San Francisco, CA 94158.
  • Shi Q; Center for Personal Dynamic Regulomes, Stanford University, Stanford, CA 94305, USA.
  • Hung KL; Center for Personal Dynamic Regulomes, Stanford University, Stanford, CA 94305, USA.
  • Samelson AJ; Institute for Neurodegenerative Diseases, University of California, San Francisco, CA 94158.
  • Pogson AN; Department of Cellular and Molecular Pharmacology, University of California, San Francisco, CA 94158, USA; Whitehead Institute for Biomedical Research, Massachusetts Institute of Technology, Cambridge 02142, USA.
  • Kim JYS; Chan Zuckerberg Biohub, San Francisco, CA 94158, USA.
  • Chung A; Department of Urology, University of California, San Francisco, CA 94158, USA; Tetrad Graduate Program, University of California, San Francisco, CA 94158, USA.
  • Leonetti MD; Chan Zuckerberg Biohub, San Francisco, CA 94158, USA.
  • Chang HY; Center for Personal Dynamic Regulomes, Stanford University, Stanford, CA 94305, USA; Howard Hughes Medical Institute, Stanford University, Stanford, CA 94305, USA.
  • Kampmann M; Institute for Neurodegenerative Diseases, University of California, San Francisco, CA 94158; Chan Zuckerberg Biohub, San Francisco, CA 94158, USA; Department of Biochemistry and Biophysics, University of California, San Francisco, CA 94158, USA.
  • Bernstein BE; Department of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02139, USA; Center for Cancer Research, Massachusetts General Hospital, Boston, MA 02129, USA.
  • Hovestadt V; Broad Institute of MIT and Harvard, Cambridge, MA 02139, USA; Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Division of Hematology/Oncology, Boston Children's Hospital, Boston, MA 02215, USA.
  • Gilbert LA; Department of Cellular and Molecular Pharmacology, University of California, San Francisco, CA 94158, USA; Department of Urology, University of California, San Francisco, CA 94158, USA; Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, CA 94158, USA. Electroni
  • Weissman JS; Department of Cellular and Molecular Pharmacology, University of California, San Francisco, CA 94158, USA; Howard Hughes Medical Institute, University of California, San Francisco, CA 94158, USA; Whitehead Institute for Biomedical Research, Massachusetts Institute of Technology, Cambridge 02142, USA
Cell ; 184(9): 2503-2519.e17, 2021 04 29.
Article in En | MEDLINE | ID: mdl-33838111
ABSTRACT
A general approach for heritably altering gene expression has the potential to enable many discovery and therapeutic efforts. Here, we present CRISPRoff-a programmable epigenetic memory writer consisting of a single dead Cas9 fusion protein that establishes DNA methylation and repressive histone modifications. Transient CRISPRoff expression initiates highly specific DNA methylation and gene repression that is maintained through cell division and differentiation of stem cells to neurons. Pairing CRISPRoff with genome-wide screens and analysis of chromatin marks establishes rules for heritable gene silencing. We identify single guide RNAs (sgRNAs) capable of silencing the large majority of genes including those lacking canonical CpG islands (CGIs) and reveal a wide targeting window extending beyond annotated CGIs. The broad ability of CRISPRoff to initiate heritable gene silencing even outside of CGIs expands the canonical model of methylation-based silencing and enables diverse applications including genome-wide screens, multiplexed cell engineering, enhancer silencing, and mechanistic exploration of epigenetic inheritance.
Subject(s)
Key words
Fulltext
Print
XML
PubMed Links
Search on Google

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Epigenesis, Genetic / Cellular Reprogramming / Induced Pluripotent Stem Cells / CRISPR-Cas Systems / Gene Editing / Epigenome / Neurons Limits: Humans Language: En Journal: Cell Year: 2021 Type: Article Affiliation country: United States
Fulltext
Print
XML
PubMed Links
Search on Google

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Epigenesis, Genetic / Cellular Reprogramming / Induced Pluripotent Stem Cells / CRISPR-Cas Systems / Gene Editing / Epigenome / Neurons Limits: Humans Language: En Journal: Cell Year: 2021 Type: Article Affiliation country: United States