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Loss Of Setdb1 Decompacts The Inactive X Chromosome In Part Through Reactivation Of An Enhancer In The Il1rapl1 Gene

Title: Loss Of Setdb1 Decompacts The Inactive X Chromosome In Part Through Reactivation Of An Enhancer In The Il1rapl1 Gene.
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Name(s): Sun, Zhuo, author
Chadwick, Brian P., author
Type of Resource: text
Genre: Journal Article
Text
Journal Article
Date Issued: 2018-08-13
Physical Form: computer
online resource
Extent: 1 online resource
Language(s): English
Abstract/Description: Background: The product of dosage compensation in female mammals is the inactive X chromosome (Xi). Xi facultative heterochromatin is organized into two different types, one of which is defined by histone H3 trimethylated at lysine 9 (H3K9me3). The rationale for this study was to assess SET domain bifurcated 1 (SETDB1) as a candidate for maintaining this repressive modification at the human Xi. Results: Here, we show that loss of SETDB1 does not result in large-scale H3K9me3 changes at the Xi, but unexpectedly we observed striking decompaction of the Xi territory. Close examination revealed a 0.5 Mb region of the Xi that transitioned from H3K9me3 heterochromatin to euchromatin within the 3' end of the IL1RAPL1 gene that is part of a common chromosome fragile site that is frequently deleted or rearranged in patients afflicted with intellectual disability and other neurological ailments. Centrally located within this interval is a powerful enhancer adjacent to an ERVL-MaLR element. In the absence of SETDB1, the enhancer is reactivated on the Xi coupled with bidirectional transcription from the ERVL-MaLR element. Xa deletion of the enhancer/ERVL-MaLR resulted in loss of full-length IL1RAPL1 transcript in cis, coupled with trans decompaction of the Xi chromosome territory, whereas Xi deletion increased detection of full-length IL1RAPL1 transcript in trans, but did not impact Xi compaction. Conclusions: These data support a critical role for SETDB1 in maintaining the ERVL-MaLR element and adjacent enhancer in the 3' end of the IL1RAPL1 gene in a silent state to facilitate Xi compaction.
Identifier: FSU_libsubv1_wos_000441459500001 (IID), 10.1186/s13072-018-0218-9 (DOI)
Keywords: human genome, transcription factor, cell-lines, X chromosome inactivation, ctcf binding, Enhancer, Euchromatin, facultative heterochromatin, h3 lysine-27 methylation, Heterochromatin, histone methyltransferase activity, il1rapl1, Inactive X chromosome, linked intellectual disability, mental-retardation, setdb1, xist rna
Publication Note: The publisher’s version of record is available at https://doi.org/10.1186/s13072-018-0218-9
Persistent Link to This Record: http://purl.flvc.org/fsu/fd/FSU_libsubv1_wos_000441459500001
Owner Institution: FSU
Is Part Of: Epigenetics & Chromatin.
1756-8935
Issue: vol. 11

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Sun, Z., & Chadwick, B. P. (2018). Loss Of Setdb1 Decompacts The Inactive X Chromosome In Part Through Reactivation Of An Enhancer In The Il1rapl1 Gene. Epigenetics & Chromatin. Retrieved from http://purl.flvc.org/fsu/fd/FSU_libsubv1_wos_000441459500001