Human DUX4 and porcine DUXC activate similar early embryonic programs in pig muscle cells: implications for preclinical models of FSHD.

Autor:	Nip Y; Division of Human Biology, Fred Hutchinson Cancer Center, Seattle, WA 98109, USA., Bennett SR; Division of Human Biology, Fred Hutchinson Cancer Center, Seattle, WA 98109, USA., Smith AA; Division of Human Biology, Fred Hutchinson Cancer Center, Seattle, WA 98109, USA., Jones TI; Department of Pharmacology, University of Nevada, Reno School of Medicine, Reno, NV 89557, USA., Jones PL; Department of Pharmacology, University of Nevada, Reno School of Medicine, Reno, NV 89557, USA., Tapscott SJ; Division of Human Biology, Fred Hutchinson Cancer Center, Seattle, WA 98109, USA.; Department of Neurology, University of Washington School of Medicine, Seattle, WA 98105, USA.
Jazyk:	angličtina
Zdroj:	Human molecular genetics [Hum Mol Genet] 2023 May 18; Vol. 32 (11), pp. 1864-1874.
DOI:	10.1093/hmg/ddad021
Abstrakt:	Human DUX4 and its mouse ortholog Dux are normally expressed in the early embryo-the 4-cell or 2-cell cleavage stage embryo, respectively-and activate a portion of the first wave of zygotic gene expression. DUX4 is epigenetically suppressed in nearly all somatic tissue, whereas facioscapulohumeral dystrophy (FSHD)-causing mutations result in its aberrant expression in skeletal muscle, transcriptional activation of the early embryonic program and subsequent muscle pathology. Although DUX4 and Dux both activate an early totipotent transcriptional program, divergence of their DNA binding domains limits the use of DUX4 expressed in mice as a preclinical model for FSHD. In this study, we identify the porcine DUXC messenger ribonucleic acid expressed in early development and show that both pig DUXC and human DUX4 robustly activate a highly similar early embryonic program in pig muscle cells. These results support further investigation of pig preclinical models for FSHD. (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)
Databáze:	MEDLINE
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