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Occupying Chromatin: Polycomb Mechanisms for Getting to Genomic Targets, Stopping Transcriptional Traffic, and Staying Put Jeffrey A. Simon, Robert E. Kingston Molecular Cell Volume 49, Issue 5, Pages (March 2013) DOI: /j.molcel Copyright © 2013 Elsevier Inc. Terms and Conditions
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Figure 1 Compositions and Activities of PcG Complexes
(A) The PRC2 family of complexes is shown. Core subunits are in lavender, and arrows depict association of optional subunits. Dashed lines indicate alternative subunits derived from multiple gene copies or protein variants from a single gene. (B–D) The PRC1 family of complexes is depicted. (B) Canonical PRC1 from Drosophila (left) and human (right) with four core subunits including a PC homolog (CBX in mammals). (C) Drosophila PRC1 variant with KDM2 subunit. (D) Human PRC1 variants that contain KDM2 and/or RYBP subunits. In human PRC1 complexes, assembly of RYBP and CBX subunits are mutually exclusive. See (Gao et al., 2012; Gearhart et al., 2006; Lagarou et al., 2008; Tavares et al., 2012) for detailed descriptions of PRC1 variants. Ubiquitylation occurs on H2AK119 in mammals, corresponding to K118 in Drosophila. (E) PHO-RC from Drosophila. (F) PR-DUB from Drosophila. Human homologs of PHO (YY1), SFMBT, ASX, and Calypso (BAP1) exist, and mammalian complexes containing ASXL1/ASXL2 and BAP1 have been described (Dey et al., 2012). Mammalian complexes comparable to fly PHO-RC have not been characterized. Molecular Cell , DOI: ( /j.molcel ) Copyright © 2013 Elsevier Inc. Terms and Conditions
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Figure 2 Optional Subunits and Chromatin Features that Modulate PRC2
(A) Domain organizations of PCLs and JARID2. (B) Features of the histone H3 tail that modulates PRC2 activity. Yellow circles denote trimethylation. PRC2 trimethylates K27; this activity is inhibited by K4me3 and K36me2/K36me3 in cis (red bars) and is stimulated by K27me3 and H3 peptide 31–42 in trans (green arrows). (C) Sites within SU(Z)12 and EED subunits (labeled S) mediate inhibition (red bars) or stimulation (green arrows) of PRC2 enzyme activity, presumably by impacting the SET domain active site (black arrows). Molecular Cell , DOI: ( /j.molcel ) Copyright © 2013 Elsevier Inc. Terms and Conditions
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Figure 3 Mechanisms of Repression by PRC1 Family Complexes
(A) Ubiquitylation of histone H2A, normally by the PRC1 variant that includes a KDM2B/FBXL10-type subunit. It is not known how ubiquitylation impacts transcription, but inhibition has been proposed to occur after initiation. (B) Compaction of the chromatin template by canonical PRC1 containing the PC/CBX and PH subunits. Compaction might occur over promoter regions, in gene bodies, or throughout the gene. (C) PRC1 interacting with the general transcription factor TFIID and blocking association of the Mediator complex required for transcriptional activation. Molecular Cell , DOI: ( /j.molcel ) Copyright © 2013 Elsevier Inc. Terms and Conditions
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Figure 4 Mechanisms of PcG Maintenance during Replication and Mitosis
(A) PRC1 is retained at the replication fork in S phase. One mechanism with biochemical support involves bridging between the PSC subunits of adjacent PRC1 complexes to maintain contact as the replication fork progresses through a region. (B) The H3K27me3 mark (red circles) binds the PRC2 complex and stimulates activity, creating a mechanism to maintain local K27me3 following replication and deposition of new nucleosomes. (C) PRC1 components remain associated with mitotic chromatin at a subset of the locations bound during other stages of the cell cycle. This might promote broader repopulation of sites by PRC1 upon G1 re-entry. Blue arrow denotes the transcription start site of a resident gene. Molecular Cell , DOI: ( /j.molcel ) Copyright © 2013 Elsevier Inc. Terms and Conditions
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