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ZFP92, a KRAB domain zinc finger protein enriched in pancreatic islets, binds to B1/Alu SINE transposable elements and regulates retroelements and genes

Osipovich, Anna B ; Dudek, Karrie D ; Trinh, Linh T ; Kim, Lily H ; Shrestha, Shristi ; Cartailler, Jean-Philippe ; Magnuson, Mark A Chuong, Edward

PLoS genetics, 2023-05, Vol.19 (5), p.e1010729-e1010729 [Periódico revisado por pares]

United States: Public Library of Science

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Título:
ZFP92, a KRAB domain zinc finger protein enriched in pancreatic islets, binds to B1/Alu SINE transposable elements and regulates retroelements and genes
Autor: Osipovich, Anna B ; Dudek, Karrie D ; Trinh, Linh T ; Kim, Lily H ; Shrestha, Shristi ; Cartailler, Jean-Philippe ; Magnuson, Mark A
Chuong, Edward
Assuntos: Animals ; Biology and Life Sciences ; Blood Glucose ; Blood levels ; Body mass ; Chromatin ; CRISPR ; Developmental stages ; DNA Transposable Elements ; Engineering and Technology ; Evolution ; Female ; Gene expression ; Genetic aspects ; Genetic research ; Genomes ; Homeostasis ; Insulin ; Islands of Langerhans ; Islets of Langerhans - metabolism ; Male ; Mammals - genetics ; Medicine and Health Sciences ; Mice ; Mutation ; Pancreas ; Physiological aspects ; Protein binding ; Proteins ; Repressor Proteins - genetics ; Retroelements - genetics ; Short interspersed nucleotide elements ; Stem cells ; Transcriptomics ; Transposons ; Zinc finger proteins ; Zinc Fingers - genetics
É parte de: PLoS genetics, 2023-05, Vol.19 (5), p.e1010729-e1010729
Notas: ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
The authors have declared that no competing interests exist.
Descrição: Repressive KRAB domain-containing zinc-finger proteins (KRAB-ZFPs) are abundant in mammalian genomes and contribute both to the silencing of transposable elements (TEs) and to the regulation of developmental stage- and cell type-specific gene expression. Here we describe studies of zinc finger protein 92 (Zfp92), an X-linked KRAB-ZFP that is highly expressed in pancreatic islets of adult mice, by analyzing global Zfp92 knockout (KO) mice. Physiological, transcriptomic and genome-wide chromatin binding studies indicate that the principal function of ZFP92 in mice is to bind to and suppress the activity of B1/Alu type of SINE elements and modulate the activity of surrounding genomic entities. Deletion of Zfp92 leads to changes in expression of select LINE and LTR retroelements and genes located in the vicinity of ZFP92-bound chromatin. The absence of Zfp92 leads to altered expression of specific genes in islets, adipose and muscle that result in modest sex-specific alterations in blood glucose homeostasis, body mass and fat accumulation. In islets, Zfp92 influences blood glucose concentration in postnatal mice via transcriptional effects on Mafb, whereas in adipose and muscle, it regulates Acacb, a rate-limiting enzyme in fatty acid metabolism. In the absence of Zfp92, a novel TE-Capn11 fusion transcript is overexpressed in islets and several other tissues due to de-repression of an IAPez TE adjacent to ZFP92-bound SINE elements in intron 3 of the Capn11 gene. Together, these studies show that ZFP92 functions both to repress specific TEs and to regulate the transcription of specific genes in discrete tissues.
Editor: United States: Public Library of Science
Idioma: Inglês

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ZFP92, a KRAB domain zinc finger protein enriched in pancreatic islets, binds to B1/Alu SINE transposable elements and regulates retroelements and genes

Osipovich, Anna B ; Dudek, Karrie D ; Trinh, Linh T ; Kim, Lily H ; Shrestha, Shristi ; Cartailler, Jean-Philippe ; Magnuson, Mark A Chuong, Edward

United States: Public Library of Science

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