Abstract
Polycomb group (PcG) proteins are key chromatin regulators implicated in multiple processes including embryonic development, tissue homeostasis, genomic imprinting, X-chromosome inactivation, and germ cell differentiation. The PcG proteins recognize target genomic loci through cis DNA sequences known as Polycomb Response Elements (PREs), which are well characterized in Drosophila. However, mammalian PREs have been elusive until two groups reported putative mammalian PREs recently. Consistent with the existence of mammalian PREs, here we report the identification and characterization of a potential PRE from human T cells. The putative human PRE has enriched binding of PcG proteins, and such binding is dependent on a key PcG component SUZ12. We demonstrate that the putative human PRE carries both genetic and molecular features of Drosophila PRE in transgenic flies, implying that not only the trans PcG proteins but also certain features of the cis PREs are conserved between mammals and Drosophila.
Highlights
Polycomb group (PcG) proteins, together with the functionally antagonizing trithorax group proteins (TrxG), maintain a predetermined state of transcription, which constitutes a cellular memory stable over many cell divisions [1,2,3,4,5,6,7,8]
PRC1 and PRC2 proteins have differential binding to the three DNA elements tested In Drosophila, PcG proteins have enriched binding at Polycomb Response Elements (PREs) sites [15,45,46,47]
In this study we sought to identify potential PREs using a candidate approach based on the hypothesis that a functional PRE is associated with H3K27me3 and PcG proteins, and is localized near silenced genes
Summary
Polycomb group (PcG) proteins, together with the functionally antagonizing trithorax group proteins (TrxG), maintain a predetermined state of transcription, which constitutes a cellular memory stable over many cell divisions [1,2,3,4,5,6,7,8]. The PcG proteins act in at least two distinct but interacting protein complexes in mammals, Polycomb Repressive Complex 1 (PRC1, containing BMI1, RING1A, RING1B, CBX, and PHC) and PRC2 (EZH2, SUZ12, and EED) [9,10]. In Drosophila, two additional PcG complexes were identified as Pho repressive complex (PhoRC, containing DNA binding proteins Pho/Phol and dSfmbt) and Polycomb repressive deubiquitinase (PR-DUB) [13,14]. A widely accepted model of PcG action is initiated by the PRC2 complex, which contains an enzymatic component EZH2 to trimethylate histone H3 at Lysine 27 (H3K27me3) [21,22,23,24]. The methylated histone recruits PRC1, which binds to H3K27me through the chromodomain of the PC (Polycomb) protein [25,26], leading to nucleation of the entire PcG complex. In contrast to the transcriptional repressive activity of the PcG complex, the active H3K4me mark is generated by the TrxG complex [2,30,31] whose function opposes the PcG function
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