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Early chromosome condensation by XIST builds A-repeat RNA density that facilitates gene silencing

Valledor, Melvys
Byron, Meg
Dumas, Brett
Carone, Dawn M
Hall, Lisa L
Lawrence, Jeanne B
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Abstract

XIST RNA triggers chromosome-wide gene silencing and condenses an active chromosome into a Barr body. Here, we use inducible human XIST to examine early steps in the process, showing that XIST modifies cytoarchitecture before widespread gene silencing. In just 2-4 h, barely visible transcripts populate the large "sparse zone" surrounding the smaller "dense zone"; importantly, density zones exhibit different chromatin impacts. Sparse transcripts immediately trigger immunofluorescence for H2AK119ub and CIZ1, a matrix protein. H3K27me3 appears hours later in the dense zone, which enlarges with chromosome condensation. Genes examined are silenced after compaction of the RNA/DNA territory. Insights into this come from the findings that the A-repeat alone can silence genes and rapidly, but only where dense RNA supports sustained histone deacetylation. We propose that sparse XIST RNA quickly impacts architectural elements to condense the largely non-coding chromosome, coalescing RNA density that facilitates an unstable, A-repeat-dependent step required for gene silencing.

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Valledor M, Byron M, Dumas B, Carone DM, Hall LL, Lawrence JB. Early chromosome condensation by XIST builds A-repeat RNA density that facilitates gene silencing. Cell Rep. 2023 Jul 25;42(7):112686. doi: 10.1016/j.celrep.2023.112686. Epub 2023 Jun 28. PMID: 37384527; PMCID: PMC10461597.

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DOI
10.1016/j.celrep.2023.112686
PubMed ID
37384527
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2023 The Authors. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).Attribution-NonCommercial-NoDerivatives 4.0 International