The CBX family of proteins in transcriptional repression and memory
- PDF / 910,719 Bytes
- 8 Pages / 595.276 x 790.866 pts Page_size
- 91 Downloads / 194 Views
Ó Indian Academy of Sciences (0123456789().,-volV) (0123456789().,-volV)
Perspectives The CBX family of proteins in transcriptional repression and memory JONGMIN KIM1,2 and ROBERT E KINGSTON1,2* 1
Department of Molecular Biology and MGH Research Institute, Massachusetts General Hospital, Boston, MA, USA 2
Department of Genetics, Harvard Medical School, Boston, MA, USA *Corresponding author (Email, [email protected])
For mammals to develop properly, master regulatory genes must be repressed appropriately in a heritable manner. This review concerns the Polycomb Repressive Complex 1 (PRC1) family and the relationship between the establishment of repression and memory of the repressed state. The primary focus is on the CBX family of proteins in PRC1 complexes and their role in both chromatin compaction and phase separation. These two activities are linked and might contribute to both repression and memory. Keywords. CBX; chromatin; epigenetic memory; nucleosome compaction; phase separation; Polycomb Repressive Complex
1. Introduction to the Polycomb-Group in mammals It is essential for proper development that master regulatory proteins be stably repressed in cell lineages where their expression would specify an inappropriate cell type. The Polycomb-Group (PcG) of genes encode several protein complexes that accomplish this repression in a wide range of organisms including flies and mammals. This system must have mechanism(s) that repress gene expression and must also have mechanism(s) that generate heritability of that repressed state over numerous cell divisions. This latter aspect, the epigenetic memory of the repressed state, must be secure or clones of cells that have incorrect cell specification would arise. This perspective focuses on recent data indicating a possible link between the mechanisms that repress and the mechanisms that generate epigenetic memory.
This article is part of the Topical Collection: Chromatin Biology and Epigenetics. http://www.ias.ac.in/jbiosci
Two major families of complexes coordinate to generate repression and epigenetic memory – the Polycomb Repressive Complex 1 (PRC1) and 2 (PRC2) families. The PRC2 family has a methyltransferase (in mammals EZH2 or less frequently EZH1) as a central component and is responsible for creating domains of methylated lysine 27 of histone H3. Both di-(H3K27me2) and trimethylation (H3K27me3) are important for regulation by the PcG (Ferrari et al. 2014; Lee et al. 2015). The PRC1 family of complexes includes two major classes, one of which is called ‘canonical’ PRC1 (cPRC1) and contains, as one subunit, a member of the CBX family, a protein that contains a chromodomain that binds to H3K27me3 (figure 1). The ‘non-canonical’ PRC1 (ncPRC1) complexes do not contain a CBX protein and generate a distinct covalent modification, ubiquitylated histone H2A, which also decorates PcG repressed domains. This ubiquitylation mark stimulates PRC2 methylation of H3K27 (Kalb et al. 2014), and thus helps propagate PcG domains (for an in-depth background, see r
Data Loading...
