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The PRC2 complex is an important member of the PcG family, and a large number of biochemical studies have suggested models for its role in mediating gene repression (reviewed in Margueron and Reinberg, 2011).
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Together these observations suggest that some polycomb repressed sites rely more specifically on KDM2B mediated RING1B occupancy for normal H2AK119ub1 and polycomb mediated gene repression (Endoh et al., 2012).
Their study demonstrated impaired placental trophoblast lineage differentiation in Alkbh1−/− mice, and a strong interaction of Alkbh1 with Mrj, an essential placental gene that mediates gene repression by recruitment of class II histone deacetylases (HDAC) [20].
Recently, lincRNA-p21 was shown to be a transcriptional target of p53 that mediates gene repression to promote apoptosis.
While FoxO could mediate gene repression through direct binding to gene promoters, as has been documented previously [ 54– 56], FoxO may also regulate gene repression through indirect mechanisms.
Indirectly, it can facilitate the binding to methylated DNA of methyl-CpG-binding domain proteins, which can mediate gene repression through interaction with histone-modifying enzymes [ 28].
In liver, H3K9me2 mediates gene repression by small heterodimer partner (SHP) 27, 28, an orphan nuclear receptor that inhibits the transcriptional activities of many nuclear receptors 29, 30.
Indeed the methylated constructs that were introduced to F9 cells lacking MeCP-1 showed partial repression, supporting our claim that other mechanisms, in addition to repression by MBPs, are involved in methylation mediated gene repression.
Evidence for a direct role for DNA methylation in NRSF/REST mediated gene suppression has also been reported [ 50] and a connection between REST binding and polycomb mediated gene repression has been established [ 51].
The addition of a methyl group to the cytosine of a CpG dinucleotide (i.e., DNA methylation) in the promoter region of genes commonly mediates gene repression and acts as a silencing mechanism [ 1].
DNA methylation promotes gene silencing either by directly blocking the binding of transcription factors to DNA or by the binding of MBPs (methyl-binding proteins, e.g., MBD1, MBD2, MBD3, and MBD4), which can mediate gene repression through interaction with a co-repressor complex [ 18, 28].
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