SHREC Silences Heterochromatin via Distinct Remodeling and Deacetylation Modules.
Nucleosome remodeling and deacetylation (NuRD) complexes are co-transcriptional regulators implicated in differentiation, development, and diseases. Methyl-CpG binding domain (MBD) proteins play an essential role in recruitment of NuRD complexes to their target sites in chromatin. The related SHREC complex in fission yeast drives transcriptional gene silencing in heterochromatin through cooperation with HP1 proteins. How remodeler and histone deacetylase (HDAC) cooperate within NuRD complexes remains unresolved. We determined that in SHREC the two modules occupy distant sites on the scaffold protein Clr1 and that repressive activity of SHREC can be modulated by the expression level of the HDAC-associated Clr1 domain alone. Moreover, the crystal structure of Clr2 reveals an MBD-like domain mediating recruitment of the HDAC module to heterochromatin. Thus, SHREC bi-functionality is organized in two separate modules with separate recruitment mechanisms, which work together to elicit transcriptional silencing at heterochromatic loci.
Department of Pathology, St. Jude Children's Research Hospital, 262 Danny Thomas Place, Memphis, TN 38105, USA.
Godwin
G
Job
Department of Molecular Biology, Science III, Institute of Genetics and Genomics of Geneva (iGE3), University of Geneva, 1211 Geneva 4, Switzerland.
Christiane
C
Brugger
Department of Pathology, St. Jude Children's Research Hospital, 262 Danny Thomas Place, Memphis, TN 38105, USA.
Tao
T
Xu
Department of Pathology, St. Jude Children's Research Hospital, 262 Danny Thomas Place, Memphis, TN 38105, USA.
Brandon R
BR
Lowe
Department of Molecular Biology, Science III, Institute of Genetics and Genomics of Geneva (iGE3), University of Geneva, 1211 Geneva 4, Switzerland.
Yvan
Y
Pfister
Department of Computational Biology, St. Jude Children's Research Hospital, 262 Danny Thomas Place, Memphis, TN 38105, USA.
Chunxu
C
Qu
Department of Pathology, St. Jude Children's Research Hospital, 262 Danny Thomas Place, Memphis, TN 38105, USA.
Sreenath
S
Shanker
Department of Molecular Biology, Science III, Institute of Genetics and Genomics of Geneva (iGE3), University of Geneva, 1211 Geneva 4, Switzerland.
José I
JI
Baños Sanz
Department of Pathology, St. Jude Children's Research Hospital, 262 Danny Thomas Place, Memphis, TN 38105, USA. Electronic address: janet.partridge@stjude.org.
Janet F
JF
Partridge
Department of Molecular Biology, Science III, Institute of Genetics and Genomics of Geneva (iGE3), University of Geneva, 1211 Geneva 4, Switzerland. Electronic address: thomas.schalch@unige.ch.
Thomas
T
Schalch
D000107:Acetylation; D001665:Binding Sites; D042002:Chromatin Assembly and Disassembly; D018899:CpG Islands; D004271:DNA, Fungal / Q000378:metabolism; D015966:Gene Expression Regulation, Fungal; D020868:Gene Silencing; D006570:Heterochromatin / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D056245:Mi-2 Nucleosome Remodeling and Deacetylase Complex / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D008958:Models, Molecular; D009707:Nucleosomes / Q000201:enzymology / Q000235:genetics; D011485:Protein Binding; D011487:Protein Conformation; D054730:Protein Interaction Domains and Motifs; D011499:Protein Processing, Post-Translational; D012331:RNA, Fungal / Q000378:metabolism; D012568:Schizosaccharomyces / Q000201:enzymology* / Q000235:genetics; D029702:Schizosaccharomyces pombe Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D013329:Structure-Activity Relationship; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic
C488801:Clr2 protein, S pombe; D004271:DNA, Fungal; D006570:Heterochromatin; D009707:Nucleosomes; D012331:RNA, Fungal; D029702:Schizosaccharomyces pombe Proteins; D014157:Transcription Factors; D056245:Mi-2 Nucleosome Remodeling and Deacetylase Complex