Trans- and cis-acting effects of Firre on epigenetic features of the inactive X chromosome.
Trans- and cis-acting effects of Firre on epigenetic features of the inactive X chromosome.
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Firre对失活X染色体表观遗传特征的反式和顺式作用效应
DOI：
10.1038/s41467-020-19879-3
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发表时间：
2020-11-27
影响因子：
16.6
通讯作者：
Disteche CM
中科院分区：
文献类型：
--
作者：
Fang H;Bonora G;Lewandowski JP;Thakur J;Filippova GN;Henikoff S;Shendure J;Duan Z;Rinn JL;Deng X;Noble WS;Disteche CM
FIRE编码一个与核组织有关的lncRNA。在这里，我们证明了从活跃的X染色体表达的Firre RNA在体细胞中保持了组蛋白H3K27me3在非活跃的X染色体(XI)上的浓缩。这种反式作用效应涉及SUZ12，反映了Firre RNA与Polycomb抑制复合体成分之间的相互作用。如果没有Firre RNA，H3K27me3在Xi上减少，并且Xi-核周位置被破坏，这可能是由于Xi上CTCF结合减少所致。我们还观察到普遍存在的基因失调，但在XI上没有。这些效应可以通过异位表达小鼠或人的FIRE/FIRE转基因来挽救，支持保守的反式作用角色。我们还发现，XI的紧密3D结构在一定程度上取决于Firre轨迹及其RNA。在常见的淋巴祖细胞和T细胞中，FIRE对H3K27me3在基因座周围26 的Mb区域的维持起顺式作用，证明了这种lncRNA的细胞类型特异性的反式和顺式作用。FIRE编码一种参与哺乳动物核组织的lncRNA。在这里，作者发现活性X染色体(Xa)上FIRE的等位基因缺失会导致非活性X染色体(Xi)上组蛋白H3K27me3的剂量依赖性丢失，以及其他反式作用效应，包括核周位置的破坏和基因表达的轻微失调。
Firre encodes a lncRNA involved in nuclear organization. Here, we show that Firre RNA expressed from the active X chromosome maintains histone H3K27me3 enrichment on the inactive X chromosome (Xi) in somatic cells. This trans-acting effect involves SUZ12, reflecting interactions between Firre RNA and components of the Polycomb repressive complexes. Without Firre RNA, H3K27me3 decreases on the Xi and the Xi-perinucleolar location is disrupted, possibly due to decreased CTCF binding on the Xi. We also observe widespread gene dysregulation, but not on the Xi. These effects are measurably rescued by ectopic expression of mouse or human Firre/FIRRE transgenes, supporting conserved trans-acting roles. We also find that the compact 3D structure of the Xi partly depends on the Firre locus and its RNA. In common lymphoid progenitors and T-cells Firre exerts a cis-acting effect on maintenance of H3K27me3 in a 26 Mb region around the locus, demonstrating cell type-specific trans- and cis-acting roles of this lncRNA. Firre encodes a lncRNA involved in nuclear organization in mammals. Here, the authors find that allelic deletion of Firre on the active X chromosome (Xa) results in dose-dependent loss of histone H3K27me3 on the inactive X chromosome (Xi), along with other trans-acting effects, including disruption of the perinuclear location and minor dysregulation of gene expression.
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影响因子：
8.8
作者：
Das PP;Hendrix DA;Apostolou E;Buchner AH;Canver MC;Beyaz S;Ljuboja D;Kuintzle R;Kim W;Karnik R;Shao Z;Xie H;Xu J;De Los Angeles A;Zhang Y;Choe J;Jun DL;Shen X;Gregory RI;Daley GQ;Meissner A;Kellis M;Hochedlinger K;Kim J;Orkin SH
通讯作者：
Orkin SH
DOI：
10.1098/rstb.2017.0021
发表时间：
2017-11-05
期刊：
Philosophical transactions of the Royal Society of London. Series B, Biological sciences
影响因子：
--
作者：
Brockdorff N
通讯作者：
Brockdorff N
影响因子：
7.7
作者：
Andergassen, Daniel;Smith, Zachary D.;Rinn, John L.
通讯作者：
Rinn, John L.
DOI：
10.1126/science.1237973
发表时间：
2013-08-16
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Engreitz JM;Pandya-Jones A;McDonel P;Shishkin A;Sirokman K;Surka C;Kadri S;Xing J;Goren A;Lander ES;Plath K;Guttman M
通讯作者：
Guttman M
影响因子：
64.8
作者：
Engreitz JM;Haines JE;Perez EM;Munson G;Chen J;Kane M;McDonel PE;Guttman M;Lander ES
通讯作者：
Lander ES