干旱区生态环境知识资源中心(Arid): Targeted chromatin conformation analysis identifies novel distal neural enhancers of ZEB2 in pluripotent stem cell differentiation

Arid

DOI	10.1093/hmg/ddaa141
	Targeted chromatin conformation analysis identifies novel distal neural enhancers of ZEB2 in pluripotent stem cell differentiation
	Birkhoff, Judith C.; Brouwer, Rutger W. W.; Kolovos, Petros; Korporaal, Anne L.; Bermejo-Santos, Ana; Boltsis, Ilias; Nowosad, Karol; van den Hout, Mirjam C. G. N.; Grosveld, Frank G.; van IJcken, Wilfred F. J.; Huylebroeck, Danny; Conidi, Andrea
通讯作者	Conidi, A
来源期刊	HUMAN MOLECULAR GENETICS
ISSN	0964-6906
EISSN	1460-2083
出版年	2020
卷号	29 期号:15 页码:2535-2550
英文摘要	The transcription factor zinc finger E-box binding protein 2 (ZEB2) controls embryonic and adult cell fate decisions and cellular maturation in many stem/progenitor cell types. Defects in these processes in specific cell types underlie several aspects of Mowat-Wilson syndrome (MOWS), which is caused by ZEB2 haplo-insufficiency. Human ZEB2, like mouse Zeb2, is located on chromosome 2 downstream of a +/- 3.5 Mb-long gene-desert, lacking any protein-coding gene. Using temporal targeted chromatin capture (T2C), we show major chromatin structural changes based on mapping in-cis proximities between the ZEB2 promoter and this gene desert during neural differentiation of human-induced pluripotent stem cells, including at early neuroprogenitor cell (NPC)/rosette state, where ZEB2 mRNA levels increase significantly. Combining T2C with histone-3 acetylation mapping, we identified three novel candidate enhancers about 500 kb upstream of the ZEB2 transcription start site. Functional luciferase-based assays in heterologous cells and NPCs reveal co-operation between these three enhancers. This study is the first to document in-cis Regulatory Elements located in ZEB2's gene desert. The results further show the usability of T2C for future studies of ZEB2 REs in differentiation and maturation of multiple cell types and the molecular characterization of newly identified MOWS patients that lack mutations in ZEB2 protein-coding exons.
类型	Article
语种	英语
开放获取类型	Green Published, Other Gold
收录类别	SCI-E
WOS记录号	WOS:000582711800007
WOS关键词	ENTERIC NERVOUS-SYSTEM ; TRANSCRIPTIONAL ENHANCERS ; HIRSCHSPRUNG-DISEASE ; NEURONAL DEVELOPMENT ; REGULATORY ELEMENTS ; MENTAL-RETARDATION ; SMAD PROTEINS ; ZFHX1B SIP1 ; GENE ; RANGE
WOS类目	Biochemistry & Molecular Biology ; Genetics & Heredity
WOS研究方向	Biochemistry & Molecular Biology ; Genetics & Heredity
资源类型	期刊论文
条目标识符	http://119.78.100.177/qdio/handle/2XILL650/327151
作者单位	[Birkhoff, Judith C.; Brouwer, Rutger W. W.; Korporaal, Anne L.; Bermejo-Santos, Ana; Boltsis, Ilias; Nowosad, Karol; van den Hout, Mirjam C. G. N.; Grosveld, Frank G.; van IJcken, Wilfred F. J.; Huylebroeck, Danny; Conidi, Andrea] Erasmus MC, Dept Cell Biol, NL-3015 CN Rotterdam, Netherlands; [Brouwer, Rutger W. W.; van den Hout, Mirjam C. G. N.; van IJcken, Wilfred F. J.] Erasmus MC, Ctr Biom, NL-3015 CN Rotterdam, Netherlands; [Kolovos, Petros] Democritus Univ Thrace, Dept Mol Biol & Genet, Alexandroupolis 68100, Greece; [Nowosad, Karol] Med Univ Lublin, Dept Biochem & Mol Biol, PL-20093 Lublin, Poland; [Huylebroeck, Danny] Katholieke Univ Leuven, Dept Dev & Regenerat, B-3000 Leuven, Belgium
推荐引用方式 GB/T 7714	Birkhoff, Judith C.,Brouwer, Rutger W. W.,Kolovos, Petros,et al. Targeted chromatin conformation analysis identifies novel distal neural enhancers of ZEB2 in pluripotent stem cell differentiation[J],2020,29(15):2535-2550.
APA	Birkhoff, Judith C..,Brouwer, Rutger W. W..,Kolovos, Petros.,Korporaal, Anne L..,Bermejo-Santos, Ana.,...&Conidi, Andrea.(2020).Targeted chromatin conformation analysis identifies novel distal neural enhancers of ZEB2 in pluripotent stem cell differentiation.HUMAN MOLECULAR GENETICS,29(15),2535-2550.
MLA	Birkhoff, Judith C.,et al."Targeted chromatin conformation analysis identifies novel distal neural enhancers of ZEB2 in pluripotent stem cell differentiation".HUMAN MOLECULAR GENETICS 29.15(2020):2535-2550.