Alu retrotransposons modulate Nanog expression through dynamic changes in regional chromatin conformation via aryl hydrocarbon receptor

Autor: Angel-Carlos Roman, Diego Muñoz-Santos, Francisco J. González-Rico, Cristina Vicente-García, Antonio Morales-Hernández, Lluis Montoliu, Almudena Fernández, Pedro M. Fernández-Salguero, Jaime M. Merino
Přispěvatelé: Ministerio de Economía y Competitividad (España), Ministerio de Ciencia, Innovación y Universidades (España), Agencia Estatal de Investigación (España), Junta de Extremadura, Red Temática de Investigación Cooperativa en Cáncer (España), Instituto de Salud Carlos III
Rok vydání: 2020
Předmět:
Homeobox protein NANOG
CCCTC-Binding Factor
Protein-Arginine N-Methyltransferases
lcsh:QH426-470
Cellular differentiation
Alu element
Alu retrotransposons
Nanog
03 medical and health sciences
Alu Elements
Cell Line
Tumor
Genetics
Humans
Molecular Biology
Aryl hydrocarbon receptor
reproductive and urinary physiology
030304 developmental biology
0303 health sciences
biology
Research
030302 biochemistry & molecular biology
Cell Differentiation
Nanog Homeobox Protein
Chromatin Assembly and Disassembly
Chromatin
Cell biology
Repressor Proteins
Chromatin Assembly Factor-1
lcsh:Genetics
Histone
Receptors
Aryl Hydrocarbon
CTCF
Differentiation
Histone methyltransferase
embryonic structures
biology.protein
Chromatin Loop
Chromatin conformation
biological phenomena
cell phenomena
and immunity
Protein Binding
Zdroj: Epigenetics & Chromatin, Vol 13, Iss 1, Pp 1-13 (2020)
Epigenetics & Chromatin
Digital.CSIC. Repositorio Institucional del CSIC
instname
ISSN: 1756-8935
Popis: © The Author(s) 2020.
Transcriptional repression of Nanog is an important hallmark of stem cell differentiation. Chromatin modifications have been linked to the epigenetic profile of the Nanog gene, but whether chromatin organization actually plays a causal role in Nanog regulation is still unclear. Here, we report that the formation of a chromatin loop in the Nanog locus is concomitant to its transcriptional downregulation during human NTERA-2 cell differentiation. We found that two Alu elements flanking the Nanog gene were bound by the aryl hydrocarbon receptor (AhR) and the insulator protein CTCF during cell differentiation. Such binding altered the profile of repressive histone modifications near Nanog likely leading to gene insulation through the formation of a chromatin loop between the two Alu elements. Using a dCAS9-guided proteomic screening, we found that interaction of the histone methyltransferase PRMT1 and the chromatin assembly factor CHAF1B with the Alu elements flanking Nanog was required for chromatin loop formation and Nanog repression. Therefore, our results uncover a chromatin-driven, retrotransposon-regulated mechanism for the control of Nanog expression during cell differentiation.
This work was supported by grants to P.M.F-S. from the Spanish Ministry of Economy and Competitiveness (SAF2014-51813-R and SAF2017-82597-R) and from the Junta de Extremadura (GR15008 and IB160210). Research at P.M.F-S. laboratory was also funded by the Red Temática de Investigación Cooperativa en Cáncer (RTICC), Carlos III Institute, Spanish Ministry of Economy and Competitiveness (RD12/0036/0032). A.C.R. was funded by a long-term FEBS Fellowship. L.M. work was funded by MINECO Grants BIO2012-39980 and BIO2015-70978-R. All Spanish funding is co-sponsored by the European Union FEDER program.
Databáze: OpenAIRE
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