{"id":758,"date":"2021-09-21T14:02:35","date_gmt":"2021-09-21T18:02:35","guid":{"rendered":"https:\/\/www.lifetein.com\/blog\/?p=758"},"modified":"2024-11-16T21:29:07","modified_gmt":"2024-11-17T02:29:07","slug":"modified-cpp-targets-essential-readers-in-h3k27m-dipg","status":"publish","type":"post","link":"https:\/\/www.lifetein.com\/blog\/modified-cpp-targets-essential-readers-in-h3k27m-dipg\/","title":{"rendered":"Modified Cell Penetrating Peptides Target Essential Readers in H3K27M-DIPG"},"content":{"rendered":"\n

Histone H3K27M is a driving mutation in diffuse intrinsic pontine glioma (DIPG), a deadly pediatric brain tumor. The malignant and treatment-resistant brain tumor is a target for anti-cancer studies using cell penetrating peptides.<\/p>\n\n\n\n


Through a global inhibition of PRC2 catalytic activity and displacement of H3K27me2\/3, H3K27M reshapes the epigenome and promotes oncogenesis of DIPG. Consequentially, the histone modification H3K36me2, antagonistic to H3K27me2\/3, is elevated. The relationship and role of H3K36me2 in H3K27M-DIPG was investigated by approaches to its upstream catalyzing enzymes, NSD1 and NSD2, the \u201cwriters\u201d, and its downstream binding factors, LEDGF and HDGF2, the \u201creaders\u201d.<\/p>\n\n\n\n


Tumor-promoting transcriptional programs in H3K27M-DIPG were found to be disrupted by loss of NSD1 and NSD2, thus impeding cellular proliferation and tumorigenesis.
Downstream, a chemically modified peptide mimicking endogenous H3K36me2 was found to dislodge LEDGF and HDGF2 from chromatin. As LEDGF and HDGF2 are the main readers mediating the protumorigenic effects downstream of NSD1\/2-H3K36me2, dislodging them resulted in inhibition of H3K27M-DIPG proliferation.<\/p>\n\n\n\n


In this study, the chemically modified peptides used were cell penetrating peptides purchased from LifeTein.<\/a>

Reference: Sci. Adv. 2021 Jul 14; 7(29)

<\/p>\n","protected":false},"excerpt":{"rendered":"

Histone H3K27M is a driving mutation in diffuse intrinsic pontine glioma (DIPG), a deadly pediatric brain tumor. The malignant and treatment-resistant brain tumor is a target for anti-cancer studies using cell penetrating peptides. 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