scholarly journals Regulation of the large ( 1000 kb) imprinted murine Ube3a antisense transcript by alternative exons upstream of Snurf/Snrpn

2004 ◽  
Vol 32 (11) ◽  
pp. 3480-3492 ◽  
Author(s):  
M. Landers
Author(s):  
Ralf S. Schmid ◽  
Xuefeng Deng ◽  
Priyalakshmi Panikker ◽  
Msema Msackyi ◽  
Camilo Breton ◽  
...  

2019 ◽  
Vol 116 (6) ◽  
pp. 2181-2186 ◽  
Author(s):  
Jack S. Hsiao ◽  
Noelle D. Germain ◽  
Andrea Wilderman ◽  
Christopher Stoddard ◽  
Luke A. Wojenski ◽  
...  

Angelman syndrome (AS) is a severe neurodevelopmental disorder caused by the loss of function from the maternal allele ofUBE3A, a gene encoding an E3 ubiquitin ligase.UBE3Ais only expressed from the maternally inherited allele in mature human neurons due to tissue-specific genomic imprinting. Imprinted expression ofUBE3Ais restricted to neurons by expression ofUBE3A antisense transcript(UBE3A-ATS) from the paternally inherited allele, which silences the paternal allele ofUBE3Aincis. However, the mechanism restrictingUBE3A-ATSexpression andUBE3Aimprinting to neurons is not understood. We used CRISPR/Cas9-mediated genome editing to functionally define a bipartite boundary element critical for neuron-specific expression ofUBE3A-ATSin humans. Removal of this element led to up-regulation ofUBE3A-ATSwithout repressing paternalUBE3A. However, increasing expression ofUBE3A-ATSin the absence of the boundary element resulted in full repression of paternalUBE3A, demonstrating thatUBE3Aimprinting requires both the loss of function from the boundary element as well as the up-regulation ofUBE3A-ATS. These results suggest that manipulation of the competition betweenUBE3A-ATSandUBE3Amay provide a potential therapeutic approach for AS.


Genes ◽  
2021 ◽  
Vol 12 (5) ◽  
pp. 759
Author(s):  
Zhongjing Su ◽  
Guangyu Liu ◽  
Bin Zhang ◽  
Ze Lin ◽  
Dongyang Huang

The leukocyte common antigen CD45 is a transmembrane phosphatase expressed on all nucleated hemopoietic cells, and the expression levels of its splicing isoforms are closely related to the development and function of lymphocytes. PEBP1P3 is a natural antisense transcript from the opposite strand of CD45 intron 2 and is predicted to be a noncoding RNA. The genotype-tissue expression and quantitative PCR data suggested that PEBP1P3 might be involved in the regulation of expression of CD45 splicing isoforms. To explore the regulatory mechanism of PEBP1P3 in CD45 expression, DNA methylation and histone modification were detected by bisulfate sequencing PCR and chromatin immunoprecipitation assays, respectively. The results showed that after the antisense RNA PEBP1P3 was knocked down by RNA interference, the DNA methylation of CD45 intron 2 was decreased and histone H3K9 and H3K36 trimethylation at the alternative splicing exons of CD45 DNA was increased. Knockdown of PEBP1P3 also increased the binding levels of chromatin conformation organizer CTCF at intron 2 and the alternative splicing exons of CD45. The present results indicate that the natural antisense RNA PEBP1P3 regulated the alternative splicing of CD45 RNA, and that might be correlated with the regulation of histone modification and DNA methylation.


2016 ◽  
Vol 43 (5) ◽  
pp. 427-436 ◽  
Author(s):  
Jiabing Sun ◽  
Xuming Wang ◽  
Chunjiang Fu ◽  
Xiaoyu Wang ◽  
Jilong Zou ◽  
...  

2006 ◽  
Vol 14 (7S_Part_29) ◽  
pp. P1547-P1548
Author(s):  
Rohan de Silva ◽  
Justyna Zareba-Paslawska ◽  
Filipa Almeida ◽  
Per Svenningsson ◽  
Tom Warner ◽  
...  

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