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PHF20 Activates Autophagy Genes through Enhancer Activation via H3K36me2 Binding Activity [RNA-seq]

ABSTRACT: Autophagy is a catabolic pathway that maintains cellular homeostasis under various stress conditions, including nutrient-deprived conditions. To elevate autophagic flux to a sufficient level under stress conditions, transcriptional activation of autophagy genes occurs to replenish autophagy components. Here, using combination of RNA-seq, ATAC-seq and ChIP-seq, we demonstrated found that plant homeodomain finger protein 20 (Phf20PHF20), which is an epigenetic reader possessing methyl binding activity, plays a key role in controlling the expression of autophagy genes. PHF20 activates autophagy genes through enhancer activation via H3K36me2 binding activity as an epigenetic reader and that our findings emphasize the importance of nuclear regulation of autophagy.

ORGANISM(S): Mus musculus

PROVIDER: GSE193392 | GEO | 2022/06/23

REPOSITORIES: GEO

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PHF20 Activates Autophagy Genes through Enhancer Activation via H3K36me2 Binding Activity [ChIP-seq]

Project description:Autophagy is a catabolic pathway that maintains cellular homeostasis under various stress conditions, including nutrient-deprived conditions. To elevate autophagic flux to a sufficient level under stress conditions, transcriptional activation of autophagy genes occurs to replenish autophagy components. Here, using combination of RNA-seq, ATAC-seq and ChIP-seq, we demonstrated found that plant homeodomain finger protein 20 (Phf20PHF20), which is an epigenetic reader possessing methyl binding activity, plays a key role in controlling the expression of autophagy genes. PHF20 activates autophagy genes through enhancer activation via H3K36me2 binding activity as an epigenetic reader and that our findings emphasize the importance of nuclear regulation of autophagy.

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PHF20 Activates Autophagy Genes through Enhancer Activation via H3K36me2 Binding Activity [ATAC-seq]

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PHF20 Activates Autophagy Genes through Enhancer Activation via H3K36me2 Binding Activity

Project description:PHF20 Activates Autophagy Genes through Enhancer Activation via H3K36me2 Binding Activity

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PHF20 Activates Autophagy Genes through Enhancer Activation via H3K36me2 Binding Activity [RNA-seq]

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PHF20 Activates Autophagy Genes through Enhancer Activation via H3K36me2 Binding Activity [ChIP-seq]

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PHF20 Activates Autophagy Genes through Enhancer Activation via H3K36me2 Binding Activity [ATAC-seq]

Project description:PHF20 Activates Autophagy Genes through Enhancer Activation via H3K36me2 Binding Activity [ATAC-seq]

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PHF20 and PHF20L1 in NSL complex

Project description:The methyl lysine readers PHF (plant homeodomain finger) 20 (PHF20) and its homolog PHF20 Like 1 (PHF20L1) are known components of the NSL (non-specific lethal) complex that regulates gene expression through its histone acetyltransferase activity. In the current model, both PHF homologs coexist in the same NSL complex although this was not formally tested; nor have the functions of PHF20 and PHF20L1 regarding NSL complex integrity and transcriptional regulation been investigated. By performing an in-depth biochemical and functional characterization, we define the association and contributions of the two methyl lysine reader homologs PHF20 and PHF20L1 to the NSL complex.

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Project description:PHF20 is a core component of the lysine acetyltransferase complex MOF-NSL that produces the major epigenetic mark, H4K16ac, and is necessary for transcriptional regulation and DNA repair, however the role of PHF20 in the complex remains elusive. Here, we report on functional crosstalk between epigenetic readers of PHF20. We show that the PHF20 PHD finger recognizes dimethylated lysine 4 of histone H3 (H3K4me2) and represents first example of a native PHD reader selective for this modification. Biochemical and structural analyses illuminate the molecular mechanism underlying this function and explain the preference of Tudor2, another reader in PHF20, for dimethylated p53. Binding of the PHD finger to H3K4me2 is required for histone acetylation, accumulation of PHF20 at target genes, and transcriptional activation. Together, our findings establish a novel PHF20-mediated link between MOF HAT, p53 and H3K4me2-dependent cellular events and suggest a model for rapid spreading of H4K16ac-encriched open chromatin.

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Identification of genes and pathways that regulated by PHF20 via gene expression profile analysis in U87 cell with PHF20 silencing

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