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Maternal Smchd1 regulates Hox gene expression and patterning in the mouse embryo [RNAseq mESC]

ABSTRACT: Maternal Smchd1 regulates Hox gene expression and patterning in the mouse embryo [RNAseq mESC]

PROVIDER: PRJNA761778 | ENA |

REPOSITORIES: ENA

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Maternal Smchd1 regulates Hox gene expression and patterning in the mouse embryo [RNAseq mESC reciprocal cross]

Project description:Parents transmit genetic and epigenetic information to their offspring. Maternal effect genes regulate the offspring epigenome to ensure normal development. Here we report that the epigenetic regulator SMCHD1 has a maternal effect on Hox gene expression and skeletal patterning. Maternal SMCHD1, present in the oocyte and preimplantation embryo, prevents precocious activation of Hox genes post-implantation. Without maternal SMCHD1, highly penetrant posterior homeotic transformations occur in the embryo. Hox genes are decorated with Polycomb marks H2AK119ub and H3K27me3 from the oocyte throughout early embryonic development; however, loss of maternal SMCHD1 does not deplete these marks. Therefore, we propose maternal SMCHD1 acts downstream of Polycomb marks to establish a chromatin state necessary for persistent epigenetic silencing and appropriate Hox gene expression later in the developing embryo. This is a striking role for maternal SMCHD1 in long-lived epigenetic effects impacting offspring phenotype. Our overall design it to compare between Smchd1 control and Smchd1 heterozygous samples. We have performed RNA-seq in a differentiation timecourse in 3 replicate mESC of each genotype with 4 timepoints, comparing the Smchd1 heterozygous to the control, at the matched timepoint.

2022-06-27 | GSE203524 | GEO

Maternal Smchd1 regulates Hox gene expression and patterning in the mouse embryo [RNAseq mESC]

2022-06-27 | GSE183736 | GEO

Maternal Smchd1 regulates Hox gene expression and patterning in the mouse embryo [ESC RRBS]

2022-06-27 | GSE203617 | GEO

Maternal Smchd1 regulates Hox gene expression and patterning in the mouse embryo [H2AK119ub CUT&RUN]

2022-06-27 | GSE183739 | GEO

Maternal Smchd1 regulates Hox gene expression and patterning in the mouse embryo [H3K27me3 CUT&RUN]

2022-06-27 | GSE183737 | GEO

Maternal Smchd1 regulates Hox gene expression and patterning in the mouse embryo [RNAseq mESC reciprocal cross]

Project description:Maternal Smchd1 regulates Hox gene expression and patterning in the mouse embryo [RNAseq mESC reciprocal cross]

| PRJNA841219 | ENA

Maternal Smchd1 regulates Hox gene expression and patterning in the mouse embryo

Project description:Maternal Smchd1 regulates Hox gene expression and patterning in the mouse embryo

| PRJNA761782 | ENA

HOX epi-mutations, driven by maternal SMCHD1 or LRIF1 haploinsufficiency, trigger homeotic transformations in genetically wildtype offspring

Project description:The body plan of animals is laid out by an evolutionary-conserved HOX code which is colinearly transcribed after zygotic genome activation (ZGA). Here we report that SMCHD1, a chromatin-modifying enzyme needed for X-inactivation in mammals, is maternally required for timely HOX expression. Using zebrafish and mouse Smchd1 knockout animals, we demonstrate that Smchd1 haplo-insufficiency brings about precocious and ectopic HOX transcription during oogenesis and embryogenesis. Unexpectedly, wild-type offspring born to heterozygous knockout zebrafish smchd1 mothers exhibited patent vertebrate patterning defects. The loss of maternal Smchd1 was accompanied by HOX epi-mutations driven by aberrant DNA methylation. We further show that this regulation is mediated by Lrif1, a direct interacting partner of Smchd1, whose knockout in zebrafish phenocopies that of Smchd1. Rather than being a short-lived maternal effect, HOX mis-regulation is stably inherited through cell divisions and persists in cultured fibroblasts derived from patients haploinsufficient for SMCHD1. We conclude that maternal Smchd1/Lrif1 sets up an epigenetic state in the HOX loci that can only be reset in the germline. Such an unusual inter-generational inheritance, whereby a phenotype can be one generation removed from its genotype, casts a new light on how unresolved Mendelian diseases may be interpreted.

2022-05-25 | GSE173462 | GEO

Maternal Smchd1 regulates Hox gene expression and patterning in the mouse embryo [RNAseq tailbud]

Project description:Maternal Smchd1 regulates Hox gene expression and patterning in the mouse embryo [RNAseq tailbud]

| PRJNA761774 | ENA

Maternal Smchd1 regulates Hox gene expression and patterning in the mouse embryo [ESC RRBS]

Project description:Maternal Smchd1 regulates Hox gene expression and patterning in the mouse embryo [ESC RRBS]

| PRJNA841596 | ENA