A protein assembly mediates Xist localization and gene silencing

Gene regulation by long non-coding RNAs and its biological functions

“…In addition, a study in mESCs has revealed that the rapid coating of the X chromosome by Xist depends on the ability of the lncRNA to exploit the 3D chromatin organization, which allows it to spread from sites that are spatially proximal to its locus to distant loci, while it modifies the target chromatin structure through its interactions with chromatin modifiers 86 . This confers XIST a role in shaping the 3D architecture of the inactivated X chromosome, a process that, once initiated, has been shown to persist even in the absence of XIST , thereby defining the role of the lncRNA as an initiator of epigenetic memory, which is maintained during the later phases of X chromosome inactivation by the protein complexes recruited by XIST to chromatin 56 , 87 , 88 .…”

Intronic Determinants Coordinate Charme lncRNA Nuclear Activity through the Interaction with MATR3 and PTBP1

“…Interestingly, MATR3 was also shown to interact with PTBP1 and with other proteins involved in splicing ( Coelho et al., 2015 ) or nuclear dynamics regulation ( Coelho et al., 2016a ) via the seven-amino-acid PTB-RRM2 Interactive (PRI) motif ( Figure 1 C, right panel). PTBP1 and MATR3 were also shown to actively bind different RNA templates, including lncRNAs, to synergistically regulate a variety of nuclear processes ( Cerase et al., 2019 ; Coelho et al., 2015 ; Pandya-Jones et al., 2020 ).…”

“…This scaffolding activity also serves for the binding of several hnRNPs that, in turn, lead to the tethering of lncRNAs to chromatin ( Garland and Jensen, 2020 ). In this scenario, paradigmatic examples have been proposed to explain how lncRNAs control the homeostasis of different aggregates, such as speckles, paraspeckles, and X chromosome condensates ( Chen et al., 2016 ; Clemson et al., 2009 ; Naganuma et al., 2012 ; Pandya-Jones et al., 2020 ; Tripathi et al., 2010 ). Notably, the binding of NEAT1 to MATR3 was proposed to regulate paraspeckle physiology and function in muscle cells ( Banerjee et al., 2017 ).…”

New Insights into X-Chromosome Reactivation during Reprogramming to Pluripotency

“…Xist RNA triggers the recruitment of a plethora of proteins that induce, propagate and stabilize the silent chromatin state on the Xi ( Figure 1 b) [ 53 , 71 , 72 , 73 ]. The molecular events involved include histone deacetylation [ 71 , 74 ], gain of Polycomb dependent chromatin marks including histone H2A lysine 119 ubiquitination (H2AK119ub1) then histone H3 lysine 27 trimethylation (H3K27me3) [ 74 , 75 , 76 , 77 ], formation of protein condensates [ 78 , 79 , 80 ], incorporation of histone variant macroH2A [ 81 , 82 ] and DNA methylation [ 83 , 84 , 85 , 86 , 87 , 88 ]. Intense research efforts have been dedicated to understanding which elements of Xist RNA are responsible for the changes in chromatin and transcription described above, which has been covered in excellent recent reviews [ 79 , 89 , 90 ].…”

“…Intense research efforts have been dedicated to understanding which elements of Xist RNA are responsible for the changes in chromatin and transcription described above, which has been covered in excellent recent reviews [ 79 , 89 , 90 ]. For example, the function of the E-repeat of Xist is delayed compared to that of the A-repeat [ 78 , 91 , 92 ]. The A-repeat appears to be the trigger for silencing while the E-repeat is important to establish stable gene silencing.…”