气候变化领域集成服务门户(CCPortal): Telomerase RNA recruits RNA polymerase II to target gene promoters to enhance myelopoiesis

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DOI	10.1073/pnas.2015528118
	Telomerase RNA recruits RNA polymerase II to target gene promoters to enhance myelopoiesis
	García-Castillo J.; Alcaraz-Pérez F.; Martínez-Balsalobre E.; García-Moreno D.; Rossmann M.P.; Fernández-Lajarín M.; Bernabé-García M.; Pérez-Oliva A.B.; Rodríguez-Cortez V.C.; Bueno C.; Adatto I.; Agarwal S.; Menéndez P.; Zon L.I.; Mulero V.; Cayuela M.
发表日期	2021
ISSN	0027-8424
卷号	118 期号:32
英文摘要	Dyskeratosis congenita (DC) is a rare inherited bone marrow failure and cancer predisposition syndrome caused by mutations in telomerase or telomeric proteins. Here, we report that zebrafish telomerase RNA (terc) binds to specific DNA sequences of master myeloid genes and controls their expression by recruiting RNA Polymerase II (Pol II). Zebrafish terc harboring the CR4-CR5 domain mutation found in DC patients hardly interacted with Pol II and failed to regulate myeloid gene expression in vivo and to increase their transcription rates in vitro. Similarly, TERC regulated myeloid gene expression and Pol II promoter occupancy in human myeloid progenitor cells. Strikingly, induced pluripotent stem cells derived from DC patients with a TERC mutation in the CR4-CR5 domain showed impaired myelopoiesis, while those with mutated telomerase catalytic subunit differentiated normally. Our findings show that TERC acts as a transcription factor, revealing a target for therapeutic intervention in DC patients. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	Dyskeratosis congenita; Myelopoiesis; Telomerase RNA component; Zebrafish
语种	英语
scopus关键词	RNA polymerase II; RNA; RNA polymerase II; telomerase; telomerase RNA; zebrafish protein; adult; animal cell; animal experiment; Article; catalysis; controlled study; DNA sequence; dyskeratosis congenita; embryo; gene; gene control; gene expression; gene function; gene interaction; gene mutation; gene targeting; genetic association; genetic transcription; human; human cell; in vitro study; in vivo study; induced pluripotent stem cell; molecular interaction; myeloid progenitor cell; myelopoiesis; nonhuman; promoter region; TERC gene; zebra fish; animal; binding site; cell culture; gene expression regulation; genetics; larva; metabolism; mutation; myelopoiesis; pathology; physiology; promoter region; protein domain; transgenic animal; Animals; Animals, Genetically Modified; Binding Sites; Cells, Cultured; Dyskeratosis Congenita; Gene Expression Regulation; Humans; Induced Pluripotent Stem Cells; Larva; Mutation; Myelopoiesis; Promoter Regions, Genetic; Protein Domains; RNA; RNA Polymerase II; Telomerase; Zebrafish; Zebrafish Proteins
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/251077
作者单位	Grupo de Telomerasa, Cáncer y Envejecimiento, Hospital Clínico Universitario Virgen de la Arrixaca, Murcia, 30120, Spain; Instituto Murciano de Investigación Biosanitaria-Arrixaca, Murcia, 30120, Spain; Centro de Investigación Biomédica en Red de Enfermedades Raras, Instituto de Salud Carlos III, Murcia, 30100, Spain; Departamento de Biología Celular e Histología, Facultad de Biología, Universidad de Murcia, Murcia, 30100, Spain; Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, United States; Stem Cell Program, Division of Hematology/Oncology, Boston Children's Hospital, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, United States; Josep Carreras Leukemia Research Institute, University of Barcelona, Barcelona, 08036, Spain; Department of Biomedicine, School of Medicine, University of Barcelona, Barcelona, 08036, Spain; Centro de Investigación Biomédica en Red de Cáncer, Instituto de Salud Carlos III, Barcelona, 08036, Spain; Instituciò C...
推荐引用方式 GB/T 7714	García-Castillo J.,Alcaraz-Pérez F.,Martínez-Balsalobre E.,et al. Telomerase RNA recruits RNA polymerase II to target gene promoters to enhance myelopoiesis[J],2021,118(32).
APA	García-Castillo J..,Alcaraz-Pérez F..,Martínez-Balsalobre E..,García-Moreno D..,Rossmann M.P..,...&Cayuela M..(2021).Telomerase RNA recruits RNA polymerase II to target gene promoters to enhance myelopoiesis.Proceedings of the National Academy of Sciences of the United States of America,118(32).
MLA	García-Castillo J.,et al."Telomerase RNA recruits RNA polymerase II to target gene promoters to enhance myelopoiesis".Proceedings of the National Academy of Sciences of the United States of America 118.32(2021).