scholarly journals Functional conservation of lncRNAJPXdespite sequence and structural divergence

2019 ◽  
Author(s):  
Heather M. Karner ◽  
Chiu-Ho Webb ◽  
Sarah Carmona ◽  
Yu Liu ◽  
Benjamin Lin ◽  
...  

SummaryLong noncoding RNAs (lncRNAs) have been identified in all eukaryotes and are most abundant in the human genome. However, the functional importance and mechanisms of action for human lncRNAs are largely unknown. Using comparative sequence, structural, and functional analyses, we characterize the evolution and molecular function of human lncRNAJPX. We find that humanJPXand its mouse homolog, lncRNAJpx, have deep divergence in their nucleotide sequences and RNA secondary structures. Despite such differences, both lncRNAs demonstrate robust binding to CTCF, a protein that is central toJpx’s role in X chromosome inactivation. In addition, our functional rescue experiment usingJpx-deletion mutant cells, shows that humanJPXcan functionally complement the loss ofJpxin mouse embryonic stem cells. Our findings support a model for functional conservation of lncRNAs independent from sequence and structural changes. The study provides mechanistic insight into the evolution of lncRNA function.




Author(s):  
Christopher M. Weber ◽  
Antonina Hafner ◽  
Simon M. G. Braun ◽  
Jacob G. Kirkland ◽  
Benjamin Z. Stanton ◽  
...  

AbstractThe mammalian SWI/SNF, or BAF complex, has a conserved and direct role in antagonizing polycomb-mediated repression. Yet, BAF appears to also promote repression by polycomb in stem cells and cancer. How BAF both antagonizes and promotes polycomb-mediated repression remains unknown. Here, we utilize targeted protein degradation to dissect the BAF-polycomb axis in embryonic stem cells on the timescale of hours. We report that rapid BAF depletion redistributes both PRC1 and PRC2 complexes from highly occupied domains, like Hox clusters, to weakly occupied sites that are normally opposed by BAF. Polycomb redistribution from highly repressed domains results in their decompaction, gain of active epigenomic features, and transcriptional derepression. Surprisingly, through dose-dependent degradation of PRC1 & PRC2 we identify both a conventional role for BAF in polycomb-mediated repression and a second mechanism acting by global redistribution of polycomb. These findings provide new mechanistic insight into the highly dynamic state of the Polycomb-Trithorax axis.



2020 ◽  
Vol 117 (36) ◽  
pp. 22331-22340
Author(s):  
Sabina Sood ◽  
Christopher M. Weber ◽  
H. Courtney Hodges ◽  
Andrey Krokhotin ◽  
Aryaman Shalizi ◽  
...  

The chromatin remodelerCHD8is among the most frequently mutated genes in autism spectrum disorder (ASD). CHD8 has a dosage-sensitive role in ASD, but when and how it becomes critical to human social function is unclear. Here, we conducted genomic analyses of heterozygous and homozygousChd8mouse embryonic stem cells and differentiated neural progenitors. We identify dosage-sensitive CHD8 transcriptional targets, sites of regulated accessibility, and an unexpected cooperation with SOX transcription factors. Collectively, our findings reveal that CHD8 negatively regulates expression of neuronal genes to maintain pluripotency and also during differentiation. Thus, CHD8 is essential for both the maintenance of pluripotency and neural differentiation, providing mechanistic insight into its function with potential implications for ASD.





RSC Advances ◽  
2021 ◽  
Vol 11 (34) ◽  
pp. 20961-20969
Author(s):  
Yunqing He ◽  
Wanli Nie ◽  
Ying Xue ◽  
Qishan Hu

Hydrosilylation or amination products? It depends on water amount and nucleophiles like excess water or produced/added amines.



Author(s):  
T. Santos ◽  
C.S.F. Gomes ◽  
L. Hennetier ◽  
V.A.F. Costa ◽  
L.C. Costa




2021 ◽  
Vol 154 (12) ◽  
pp. 124313
Author(s):  
L. M. Hunnisett ◽  
P. F. Kelly ◽  
S. Bleay ◽  
F. Plasser ◽  
R. King ◽  
...  


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