Functional elements of the cis-regulatory lincRNA-p21

被引：27

作者：

Winkler, Lauren ^{[1
]}

Jimenez, Maria ^{[1
]}

Zimmer, Joshua T. ^{[2
,3
]}

Williams, Adam ^{[4
]}

Simon, Matthew D. ^{[2
,3
]}

Dimitrova, Nadya ^{[1
]}

机构：

[1] Yale Univ, Dept Mol Cellular & Dev Biol, New Haven, CT 06511 USA

[2] Yale Univ, Dept Mol Biophys & Biochem, New Haven, CT 06511 USA

[3] Yale Univ, Inst Biomol Design & Discovery, West Haven, CT 06516 USA

[4] Jackson Lab Genom Med, Farmington, CT 06032 USA

来源：

CELL REPORTS | 2022年 / 39卷 / 03期

关键词：

NONCODING RNAS; TRANSCRIPTION; ENHANCER; LNCRNA; COMPARTMENTALIZATION; RECRUITMENT; EXPRESSION; REVEALS; DNA;

D O I：

10.1016/j.celrep.2022.110687

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

The p53-induced long noncoding RNA (lncRNA) lincRNA-p21 is proposed to act in cis to promote p53-dependent expression of the neighboring cell cycle gene, Cdkn1a/p21. The molecular mechanism through which the transcribed lincRNA-p21 regulatory locus activates p21 expression remains poorly understood. To elucidate the functional elements of cis-regulation, we generate a series of genetic models that disrupt DNA regulatory elements, the transcription of lincRNA-p21, or the accumulation of mature lincRNA-p21. Unexpectedly, we determine that full-length transcription, splicing, and accumulation of lincRNA-p21 are dispensable for the chromatin organization of the locus and for cis-regulation. Instead, we find that production of lincRNA-p21 through conserved regions in exon 1 of lincRNA-p21 promotes cis-activation. These findings demonstrate that the activation of nascent transcription from this lncRNA locus, but not the generation or accumulation of a mature lncRNA transcript, is necessary to enact local gene expression control.

引用

页数：14

共 50 条

[41] LincRNA-p21 enhances the sensitivity of radiotherapy for human colorectal cancer by targeting the Wnt/β-catenin signaling pathway [J].

Wang, Guangyu ;

Li, Zhiwei ;

Zhao, Qi ;

Zhu, Yuanyuan ;

Zhao, Ci ;

Li, Xin ;

Ma, Zhigang ;

Li, Xiaobo ;

Zhang, Yanqiao .

ONCOLOGY REPORTS, 2014, 31 (04) :1839-1845

[42] LincRNA-p21 acts as a mediator of ING1b-induced apoptosis [J].

Tran, U. M. ;

Rajarajacholan, U. ;

Soh, J. ;

Kim, T-sS ;

Thalappilly, S. ;

Sensen, C. W. ;

Riabowol, K. .

CELL DEATH & DISEASE, 2015, 6 :e1668-e1668

[43] Direct characterization of cis-regulatory elements and functional dissection of complex genetic associations using HCR-FlowFISH [J].

Reilly, Steven K. ;

Gosai, Sager J. ;

Gutierrez, Alan ;

Mackay-Smith, Ava ;

Ulirsch, Jacob C. ;

Kanai, Masahiro ;

Mouri, Kousuke ;

Berenzy, Daniel ;

Kales, Susan ;

Butler, Gina M. ;

Gladden-Young, Adrianne ;

Bhuiyan, Redwan M. ;

Stitzel, Michael L. ;

Finucane, Hilary K. ;

Sabeti, Pardis C. ;

Tewhey, Ryan .

NATURE GENETICS, 2021, 53 (08) :1166-+

[44] Evolution of cis-regulatory elements in yeast de novo and duplicated new genes [J].

Tsai, Zing Tsung-Yeh ;

Tsai, Huai-Kuang ;

Cheng, Jen-Hao ;

Lin, Chih-Hsu ;

Tsai, Yuan-Fan ;

Wang, Daryi .

BMC GENOMICS, 2012, 13

[45] Bioinformatic Evaluation of Features on Cis-regulatory Elements at 6q25.1 [J].

Sreekar, N. ;

Shrestha, Smeeta .

BIOINFORMATICS AND BIOLOGY INSIGHTS, 2023, 17

[46] Global identification of the genetic networks and cis-regulatory elements of the cold response in zebrafish [J].

Hu, Peng ;

Liu, Mingli ;

Zhang, Dong ;

Wang, Jinfeng ;

Niu, Hongbo ;

Liu, Yimeng ;

Wu, Zhichao ;

Han, Bingshe ;

Zhai, Wanying ;

Shen, Yu ;

Chen, Liangbiao .

NUCLEIC ACIDS RESEARCH, 2015, 43 (19) :9198-9213

[47] Characterization of Cis-Regulatory Elements for Fgf10 Expression in the Chick Embryo [J].

Kawakami, Hiroko ;

Johnson, Austin ;

Fujita, Yu ;

Swearer, Avery ;

Wada, Naoyuki ;

Kawakami, Yasuhiko .

DEVELOPMENTAL DYNAMICS, 2018, 247 (12) :1253-1263

[48] Functional analysis of the evolutionarily conserved cis-regulatory elements on the sox17 gene in zebrafish [J].

Chan, Tzu-Min ;

Chao, Chung-Hao ;

Wang, Horng-Dar ;

Yu, Yen-Ju ;

Yuh, Chiou-Hwa .

DEVELOPMENTAL BIOLOGY, 2009, 326 (02) :456-470

[49] Functional characterisation of cis-regulatory elements governing dynamic Eomes expression in the early mouse embryo [J].

Simon, Claire S. ;

Downes, Damien J. ;

Gosden, Matthew E. ;

Telenius, Jelena ;

Higgs, Douglas R. ;

Hughes, Jim R. ;

Costello, Ita ;

Bikoff, Elizabeth K. ;

Robertson, Elizabeth J. .

DEVELOPMENT, 2017, 144 (07) :1249-1260

[50] Identification of functional cis-regulatory elements by sequential enrichment from a randomized synthetic DNA library [J].

Roccaro, Mario ;

Ahmadinejad, Nahal ;

Colby, Thomas ;

Somssich, Imre E. .

BMC PLANT BIOLOGY, 2013, 13

← 1 2 3 4 5 →