WFRF:(Papanicolaou N)
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| Fältnamn | Indikatorer | Metadata |
|---|---|---|
| 000 | 02819naa a2200349 4500 | |
| 001 | oai:prod.swepub.kib.ki.se:149303121 | |
| 003 | SwePub | |
| 008 | 240701s2022 | |||||||||||000 ||eng| | |
| 024 | 7 | a http://kipublications.ki.se/Default.aspx?queryparsed=id:1493031212 URI |
| 024 | 7 | a https://doi.org/10.1038/s41467-022-29414-12 DOI |
| 040 | a (SwePub)ki | |
| 041 | a engb eng | |
| 042 | 9 SwePub | |
| 072 | 7 | a ref2 swepub-contenttype |
| 072 | 7 | a art2 swepub-publicationtype |
| 100 | 1 | a Lentini, Au Karolinska Institutet4 aut |
| 245 | 1 0 | a Elastic dosage compensation by X-chromosome upregulation |
| 264 | c 2022-04-06 | |
| 264 | 1 | b Springer Science and Business Media LLC,c 2022 |
| 520 | a X-chromosome inactivation and X-upregulation are the fundamental modes of chromosome-wide gene regulation that collectively achieve dosage compensation in mammals, but the regulatory link between the two remains elusive and the X-upregulation dynamics are unknown. Here, we use allele-resolved single-cell RNA-seq combined with chromatin accessibility profiling and finely dissect their separate effects on RNA levels during mouse development. Surprisingly, we uncover that X-upregulation elastically tunes expression dosage in a sex- and lineage-specific manner, and moreover along varying degrees of X-inactivation progression. Male blastomeres achieve X-upregulation upon zygotic genome activation while females experience two distinct waves of upregulation, upon imprinted and random X-inactivation; and ablation of Xist impedes female X-upregulation. Female cells carrying two active X chromosomes lack upregulation, yet their collective RNA output exceeds that of a single hyperactive allele. Importantly, this conflicts the conventional dosage compensation model in which naïve female cells are initially subject to biallelic X-upregulation followed by X-inactivation of one allele to correct the X dosage. Together, our study provides key insights to the chain of events of dosage compensation, explaining how transcript copy numbers can remain remarkably stable across developmental windows wherein severe dose imbalance would otherwise be experienced by the cell. | |
| 700 | 1 | a Cheng, HT4 aut |
| 700 | 1 | a Noble, JC4 aut |
| 700 | 1 | a Papanicolaou, N4 aut |
| 700 | 1 | a Coucoravas, C4 aut |
| 700 | 1 | a Andrews, Nu Karolinska Institutet4 aut |
| 700 | 1 | a Deng, QLu Karolinska Institutet4 aut |
| 700 | 1 | a Enge, Mu Karolinska Institutet4 aut |
| 700 | 1 | a Reinius, Bu Karolinska Institutet4 aut |
| 710 | 2 | a Karolinska Institutet4 org |
| 773 | 0 | t Nature communicationsd : Springer Science and Business Media LLCg 13:1, s. 1854-q 13:1<1854-x 2041-1723 |
| 856 | 4 8 | u http://kipublications.ki.se/Default.aspx?queryparsed=id:149303121 |
| 856 | 4 8 | u https://doi.org/10.1038/s41467-022-29414-1 |
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- Lentini, A
- Cheng, HT
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