SMYD5 regulates H4K20me3-marked heterochromatin to safeguard ES cell self-renewal and prevent spurious differentiation [RNA-Seq]

UID: 10655

Author(s): Kidder, Benjamin L., Zhao, Keji

Description: Summary from the GEO: "Epigenetic regulation of chromatin states is thought to control the self-renewal and differentiation of embryonic stem (ES) cells. However, the roles of repressive histone modifications such as trimethylated histone lysine 20 (H4K20me3) in pluripotency and development are largely unknown. Here, we show that the histone lysine methyltransferase SMYD5 mediates H4K20me3 at heterochromatin regions. Depletion of SMYD5 leads to compromised self-renewal, including dysregulated expression of OCT4 targets, and perturbed differentiation. SMYD5 bound regions are enriched with repetitive DNA elements. Knockdown of SMYD5 results in a global decrease of H4K20me3 levels, a redistribution of heterochromatin constituents including H3K9me3/2, G9a, and HP1α, and de-repression of endogenous retroelements. A loss of SMYD5-dependent silencing of heterochromatin nearby genic regions leads to upregulated expression of lineage-specific genes, thus contributing to the decreased self-renewal and accelerated differentiation of SMYD5-depeleted ES cells. Altogether, these findings implicate a role for SMYD5 in regulating ES cell self-renewal and H4K20me3-marked heterochromatin."

Overall design from the GEO: "RNA-Seq of undifferentiated and differentiated murine shLuc and shSmyd5 ES cells"

Subject of Study

Subject(s)

Access via GEO
BEDGRAPH and RPKM files of expression profiling by high throughput sequencing
Accession #: GSE94085

Access via SRA
RNA Sequence reads for 10 samples
Accession #: SRP097856

Access via BioProject
Additional information about overall initiative.
Accession #: PRJNA368814
Access Restrictions: Free to All
Access Instructions: The NCBI Gene Expression Omnibus, SRA, and BioProject databases provide open access to these files.
Associated Publications: Ren W, Fan H, Grimm S, et al. Direct readout of heterochromatic H3K9me3 regulates DNMT1-mediated maintenance DNA methylation. Proceedings of the National Academy of Sciences of the United States of America. 2020; 117(31):18439-18447.

Kidder BL, Hu G, Cui K, Zhao K. SMYD5 regulates H4K20me3-marked heterochromatin to safeguard ES cell self-renewal and prevent spurious differentiation. Epigenetics Chromatin. 2017;10:8. Published 2017 Feb 23.
Data Type: Genomic
Equipment Used: Illumina HiSeq 2000
High throughput gene sequencing system
Software Used: SRA Toolkit
The NCBI SRA Toolkit enables reading ("dumping") of sequencing files from the SRA database and writing ("loading") files into the .sra format.
Dataset Format(s): TAR, RPKM, BEDGRAPH
Data Tool(s): RNA Seq
Dataset Size: 157.8 MB (TAR of BEDGRAPH, RPKM), 14.7 (SRA)

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