lncRNA DIGIT and BRD3 protein form phase-separated condensates to regulate endoderm differentiation

被引：105

作者：

Daneshvar, Kaveh ^{[1
,2
]}

Ardehali, M. Behfar ^{[3
,4
,5
]}

Klein, Isaac A. ^{[6
,7
]}

Hsieh, Fu-Kai ^{[3
,4
,5
]}

Kratkiewicz, Arcadia J. ^{[1
,2
]}

Mahpour, Amin ^{[1
,2
]}

Cancelliere, Sabrina O. L. ^{[2
,8
]}

Zhou, Chan ^{[1
,2
]}

Cook, Brett M. ^{[9
]}

Li, Wenyang ^{[1
,2
]}

Pondick, Joshua, V ^{[1
,2
]}

Gupta, Sweta K. ^{[1
,2
]}

Moran, Sean P. ^{[1
,2
]}

Young, Richard A. ^{[6
,10
]}

Kingston, Robert E. ^{[3
,4
,5
]}

Mullen, Alan C. ^{[1
,2
,8
]}

机构：

[1] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA

[2] Harvard Med Sch, Boston, MA 02115 USA

[3] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA

[4] Massachusetts Gen Hosp, MGH Res Inst, Boston, MA 02114 USA

[5] Harvard Med Sch, Dept Genet, Boston, MA 02115 USA

[6] Whitehead Inst Biomed Res, 9 Cambridge Ctr, Cambridge, MA 02142 USA

[7] Harvard Med Sch, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA

[8] Harvard Stem Cell Inst, Cambridge, MA USA

[9] Opt Biosyst Inc, Santa Clara, CA USA

[10] MIT, Dept Biol, 77 Massachusetts Ave, Cambridge, MA USA

来源：

NATURE CELL BIOLOGY | 2020年 / 22卷 / 10期

关键词：

LONG NONCODING RNAS; DEFINITIVE ENDODERM; SELF-ORGANIZATION; STEM-CELLS; CHROMATIN; DOMAINS; RECOGNITION; EXPRESSION; GRANULES; NEAT1;

D O I：

10.1038/s41556-020-0572-2

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Daneshvar et al. show that BRD3 and the lncRNA DIGIT form phase-separated condensates at genomic regions with H3K18ac to co-regulate the transcription of genes that drive endoderm differentiation. Cooperation between DNA, RNA and protein regulates gene expression and controls differentiation through interactions that connect regions of nucleic acids and protein domains and through the assembly of biomolecular condensates. Here, we report that endoderm differentiation is regulated by the interaction between the long non-coding RNA (lncRNA) DIGIT and the bromodomain and extraterminal domain protein BRD3. BRD3 forms phase-separated condensates of which the formation is promoted by DIGIT, occupies enhancers of endoderm transcription factors and is required for endoderm differentiation. BRD3 binds to histone H3 acetylated at lysine 18 (H3K18ac) in vitro and co-occupies the genome with H3K18ac. DIGIT is also enriched in regions of H3K18ac, and the depletion of DIGIT results in decreased recruitment of BRD3 to these regions. Our findings show that cooperation between DIGIT and BRD3 at regions of H3K18ac regulates the transcription factors that drive endoderm differentiation and suggest that protein-lncRNA phase-separated condensates have a broader role as regulators of transcription.

引用

页码：1211 / +

页数：32

共 72 条

[1]

Abmayr Susan M, 2006, Curr Protoc Mol Biol, VChapter 12, DOI [10.1002/0471141755.ph1203s35, 10.1002/0471142727.mb1201s75]

[2] Differential Association of Chromatin Proteins Identifies BAF60a/SMARCD1 as a Regulator of Embryonic Stem Cell Differentiation [J].

Alajem, Adi ;

Biran, Alva ;

Harikumar, Arigela ;

Sailaja, Badi Sri ;

Aaronson, Yair ;

Livyatan, Ilana ;

Nissim-Rafinia, Malka ;

Sommer, Andreia Gianotti ;

Mostoslavsky, Gustavo ;

Gerbasi, Vincent R. ;

Golden, Daniel E. ;

Datta, Arnab ;

Sze, Siu Kwan ;

Meshorer, Eran .

CELL REPORTS, 2015, 10 (12) :2019-2031

[3] HTSeq-a Python']Python framework to work with high-throughput sequencing data [J].

Anders, Simon ;

Pyl, Paul Theodor ;

Huber, Wolfgang .

BIOINFORMATICS, 2015, 31 (02) :166-169

[4] Bleach gel: A simple agarose gel for analyzing RNA quality [J].

Aranda, Patrick S. ;

LaJoie, Dollie M. ;

Jorcyk, Cheryl L. .

ELECTROPHORESIS, 2012, 33 (02) :366-369

[5] Biomolecular condensates: organizers of cellular biochemistry [J].

Banani, Salman F. ;

Lee, Hyun O. ;

Hyman, Anthony A. ;

Rosen, Michael K. .

NATURE REVIEWS MOLECULAR CELL BIOLOGY, 2017, 18 (05) :285-298

[6]

BELL CC, 2016, SCI REP, V6

[7] Transcription Factors Activate Genes through the Phase-Separation Capacity of Their Activation Domains [J].

Boija, Ann ;

Klein, Isaac A. ;

Sabari, Benjamin R. ;

Dall'Agnese, Alessandra ;

Coffey, Eliot L. ;

Zamudio, Alicia V. ;

Li, Charles H. ;

Shrinivas, Krishna ;

Manteiga, John C. ;

Hannett, Nancy M. ;

Abraham, Brian J. ;

Afeyan, Lena K. ;

Guo, Yang E. ;

Rimel, Jenna K. ;

Fant, Charli B. ;

Schuijers, Jurian ;

Lee, Tong Ihn ;

Taatjes, Dylan J. ;

Young, Richard A. .

CELL, 2018, 175 (07) :1842-+

[8] An Efficient Low Cost Method for Gene Transfer to T Lymphocytes [J].

Chicaybam, Leonardo ;

Sodre, Andressa Laino ;

Curzio, Bianca Azevedo ;

Bonamino, Martin Hernan .

PLOS ONE, 2013, 8 (03)

[9] Histone H3K27ac separates active from poised enhancers and predicts developmental state [J].

Creyghton, Menno P. ;

Cheng, Albert W. ;

Welstead, G. Grant ;

Kooistra, Tristan ;

Carey, Bryce W. ;

Steine, Eveline J. ;

Hanna, Jacob ;

Lodato, Michael A. ;

Frampton, Garrett M. ;

Sharp, Phillip A. ;

Boyer, Laurie A. ;

Young, Richard A. ;

Jaenisch, Rudolf .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2010, 107 (50) :21931-21936

[10]

CUATRECASAS P, 1967, J BIOL CHEM, V242, P1541

← 1 2 3 4 5 6 7 8 →