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NFIA determines the cis-effect of genetic variation on adipocyte browning in mice

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Mus musculus

PROVIDER: GSE188263 | GEO | 2022/07/27

REPOSITORIES: GEO

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NFIA determines the cis-effect of genetic variation on adipocyte browning in mice [WGS]

Project description:Thermogenic brown and beige adipocytes counteract obesity by enhancing energy dissipation via uncoupling proein-1 (Ucp1). However, the effect of genetic variation on these cells, a major source of disease susceptibility, has been less well studied. Here we examined beige adipocytes from obesity-prone C57BL/6J (B6) and obesity-resistant 129X1/SvJ (129) mouse strains and identified a cis-regulatory variant rs47238345 that is responsible for differential Ucp1 expression. The alternative T allele of rs47238345 at the Ucp1 -12kb enhancer in 129 facilitates the allele-specific binding of nuclear factor I-A (NFIA) to mediate allele-specific enhancer-promoter interaction and Ucp1 transcription. We also identified Lim homeobox protein 8 (Lhx8), whose expression is higher in 129 than in B6, as a trans-acting regulator of Ucp1 in mice and humans. These results demonstrate the cis- and trans-acting effects of genetic variation on Ucp1 expression that underlie phenotypic diversity.

2022-07-27 | GSE188261 | GEO

NFIA determines the cis-effect of genetic variation on adipocyte browning in mice [HiC]

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NFIA determines the cis-effect of genetic variation on adipocyte browning in mice [ChIP-Seq]

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NFIA determines the cis-effect of genetic variation on adipocyte browning in mice [RNA-Seq]

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NFIA determines the cis-effect of genetic variation on adipocyte browning in mice

Project description:NFIA determines the cis-effect of genetic variation on adipocyte browning in mice

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NFIA determines the cis-effect of genetic variation on adipocyte browning in mice [WGS]

Project description:NFIA determines the cis-effect of genetic variation on adipocyte browning in mice [WGS]

| PRJNA778094 | ENA

NFIA determines the cis-effect of genetic variation on adipocyte browning in mice [HiC]

Project description:NFIA determines the cis-effect of genetic variation on adipocyte browning in mice [HiC]

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NFIA determines the cis-effect of genetic variation on adipocyte browning in mice [RNA-Seq]

Project description:NFIA determines the cis-effect of genetic variation on adipocyte browning in mice [RNA-Seq]

| PRJNA776727 | ENA

NFIA determines the cis-effect of genetic variation on adipocyte browning in mice [ChIP-Seq]

Project description:NFIA determines the cis-effect of genetic variation on adipocyte browning in mice [ChIP-Seq]

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NFIA determines the <i>cis</i>-effect of genetic variation on Ucp1 expression in murine thermogenic adipocytes.

Project description:Thermogenic brown and beige adipocytes counteract obesity by enhancing energy dissipation via uncoupling protein-1 (Ucp1). However, the effect of genetic variation on these cells, a major source of disease susceptibility, has been less well studied. Here we examined beige adipocytes from obesity-prone C57BL/6J (B6) and obesity-resistant 129X1/SvJ (129) mouse strains and identified a cis-regulatory variant rs47238345 that is responsible for differential Ucp1 expression. The alternative T allele of rs47238345 at the Ucp1 -12kb enhancer in 129 facilitates the allele-specific binding of nuclear factor I-A (NFIA) to mediate allele-specific enhancer-promoter interaction and Ucp1 transcription. Furthermore, CRISPR-Cas9/Cpf1-mediated single nucleotide polymorphism (SNP) editing of rs47238345 resulted in increased Ucp1 expression. We also identified Lim homeobox protein 8 (Lhx8), whose expression is higher in 129 than in B6, as a trans-acting regulator of Ucp1 in mice and humans. These results demonstrate the cis- and trans-acting effects of genetic variation on Ucp1 expression that underlie phenotypic diversity.

| S-EPMC9304612 | biostudies-literature

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