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A satellite DNA array barcodes chromosome 7 and regulates totipotency via ZFP819.

ABSTRACT: Mammalian genomes are a battleground for genetic conflict between repetitive elements and KRAB-zinc finger proteins (KZFPs). We asked whether KZFPs can regulate cell fate by using ZFP819, which targets a satellite DNA array, ZP3AR. ZP3AR coats megabase regions of chromosome 7 encompassing genes encoding ZSCAN4, a master transcription factor of totipotency. Depleting ZFP819 in mouse embryonic stem cells (mESCs) causes them to transition to a 2-cell (2C)-like state, whereby the ZP3AR array switches from a poised to an active enhancer state. This is accompanied by a global erosion of heterochromatin roadblocks, which we link to decreased SETDB1 stability. These events result in transcription of active LINE-1 elements and impaired differentiation. In summary, ZFP819 and TRIM28 partner up to close chromatin across Zscan4, to promote exit from totipotency. We propose that satellite DNAs may control developmental fate transitions by barcoding and switching off master transcription factor genes.

SUBMITTER: Fernandes LP

PROVIDER: S-EPMC9616502 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature

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A satellite DNA array barcodes chromosome 7 and regulates totipotency via ZFP819.

Fernandes Liane P LP Enriquez-Gasca Rocio R Gould Poppy A PA Holt James H JH Conde Lucia L Ecco Gabriela G Herrero Javier J Gifford Robert R Trono Didier D Kassiotis George G Rowe Helen M HM

Science advances 20221028 43

Mammalian genomes are a battleground for genetic conflict between repetitive elements and KRAB-zinc finger proteins (KZFPs). We asked whether KZFPs can regulate cell fate by using ZFP819, which targets a satellite DNA array, ZP3AR. ZP3AR coats megabase regions of chromosome 7 encompassing genes encoding ZSCAN4, a master transcription factor of totipotency. Depleting ZFP819 in mouse embryonic stem cells (mESCs) causes them to transition to a 2-cell (2C)-like state, whereby the ZP3AR array switche ...[more]

PMID: 36306355

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Project description:The genus Pseudis comprises six frogs of the family Hylidae and only P. tocantins had heteromorphic sex chromosomes detected by classical cytogenetics. In this species, the W chromosome is larger than the Z chromosome and has a large heterochromatic block located between the centromere and the nucleolus organizer region (NOR) in the long arm. This large heterochromatic band is enriched for the PcP190 satellite DNA (satDNA), whereas the Z chromosome bears a smaller C-band adjacent to the centromere in the long arm that is not detected by PcP190 probes. To assess sex chromosome differentiation in the genus Pseudis, we investigated the PcP190 satDNA in P. bolbodactyla, P. cardosoi, P. minuta, and P. paradoxa and in one species of Lysapsus, which is the sister genus of Pseudis. PcP190 sequences were isolated, sequenced, and the diversity of this class of satDNA was analyzed. To evaluate whether sex-related variations in PcP190 satDNA were present, we used in situ hybridization (for P. bolbodactyla, P. paradoxa, P. cardosoi, and P. minuta) and Southern blotting analysis (for all species). We found a low level of sex chromosome heteromorphism in P. bolbodactyla, as a PcP190 cluster was detected in the short arm of one of the homologs of pair 7 exclusively in females. In P. paradoxa, P. minuta, and P. cardosoi, PcP190 satDNA is not sex-related, although a cluster of PcP190 sequences could be recognized in the NOR-bearing chromosomes 7 of P. paradoxa and P. minuta and their homologous chromosome 5 of P. cardosoi. By tracking cytogenetic data in a species tree, we may hypothesize that the positioning of the PcP190 site adjacently to the NOR (as observed in the long arm of the W chromosome of P. tocantins) is a derived condition with respect to the location of the PcP190 site apart from the NOR, in the short arm of the NOR-bearing chromosomes 7 (as present in P. bolbodactyla, P. paradoxa, and P. minuta) or 5 (as present in P. cardosoi) and we discuss about the emergence of PcP190 satDNA as a sex-related trait.

Dataset Information

A satellite DNA array barcodes chromosome 7 and regulates totipotency via ZFP819.

Publications

A satellite DNA array barcodes chromosome 7 and regulates totipotency via ZFP819.

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