2017
DOI: 10.1016/j.cell.2017.07.041
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Dynamic Control of X Chromosome Conformation and Repression by a Histone H4K20 Demethylase

Abstract: Summary Chromatin modification and higher-order chromosome structure play key roles in gene regulation, but their functional interplay in controlling gene expression is elusive. We discovered the machinery and mechanism underlying the dynamic enrichment of histone modification H4K20me1 on hermaphrodite X chromosomes during C. elegans dosage compensation and demonstrated H4K20me1's pivotal role in regulating higher-order chromosome structure and X-chromosome-wide gene expression. Structure and activity of dosag… Show more

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Cited by 75 publications
(184 citation statements)
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References 76 publications
(129 reference statements)
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“…In addition, demethylation of histone H4 lysine 20 to monomethyl by Dpy-21 is enhanced on the Xi chromosome in C. elegans (Brejc et al, 2017). Furthermore, many of the genes that escape inactivation in SCA karyotypes are upregulated in polyploid X karyotypes are chromatin remodelers , allowing for the possibility that as X copy number increases, repressive chromatin remodelers are deposited on the Xa chromosome, leading to the overall higher order structural changes we observe in the Xa and Xi chromosomes in SCA karyotypes.…”
Section: Discussionmentioning
confidence: 98%
“…In addition, demethylation of histone H4 lysine 20 to monomethyl by Dpy-21 is enhanced on the Xi chromosome in C. elegans (Brejc et al, 2017). Furthermore, many of the genes that escape inactivation in SCA karyotypes are upregulated in polyploid X karyotypes are chromatin remodelers , allowing for the possibility that as X copy number increases, repressive chromatin remodelers are deposited on the Xa chromosome, leading to the overall higher order structural changes we observe in the Xa and Xi chromosomes in SCA karyotypes.…”
Section: Discussionmentioning
confidence: 98%
“…In the dpy-21 mutant, the level of H4pan-ac increases specifically on the X, but H4K16ac and H3ac do not ( Figure 3J). Greater variability in the dpy-21 mutant compared to dpy-27 RNAi may be due to additional dpy-21 activity outside dosage compensation [8,18]. For H4K16ac, an X-specific effect at the TSS, but not at top 1% H4K16ac sites suggests spatial specificity for DCC-mediated reduction of H4K16ac.…”
Section: Modulates the Levels Of Active Histone Modifications On mentioning
confidence: 99%
“…DCC mediated repression appears to be chromosome-wide, with no large groups of genes escaping from dosage compensation [8,9]. Previous work has highlighted multiple roles for the DCC in regulation of X chromosome structure; DCC is required for the ~40% compaction of the X compared to autosomes [15], the regulation of subnuclear localization of the X chromosomes [16,17], and the regulation of topologically associating domains (TAD) on the X [18,19]. The DCC was also shown to increase and decrease the levels of H4K20me1 and H4K16ac, respectively, on the X chromosomes [20,21].…”
Section: Introductionmentioning
confidence: 99%
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“…The PTPN22 gene encodes the lymphoid phosphatase LYP (or PTPN22) that belongs to the protein tyrosine phosphatases (PTP) family and regulates the activity and effector functions of multiple immune cell types (Brownlie, Zamoyska, & Salmond, ). An additional gene located in the 1p13.2 region is RSBN1, whose ortholog in the mouse, Rsbn1 (also named Rosbin or KDM9), has been shown to encode the lysine‐specific histone demethylase 9 that specifically demethylates the dimethylated lysine 20 of histone H4 (H4K20me2), thereby modulating chromosome architecture (Brejc et al., ). Epigenetic alterations have been implicated in the development of rheumatoid arthritis and other autoimmune diseases (Jia et al., ); however, the RSBN1 gene has not yet been considered a candidate in studies of complex diseases.…”
Section: Introductionmentioning
confidence: 99%