David Shechter

Histone succinylation directly inhibits Jumonji domain demethylases and stabilizes repressive chromatin states

This study identifies histone succinylation as an inhibitor of JmjC demethylases, leading to stabilized repressive chromatin states and reduced transcription.

The GNMT N-terminus Couples Folate Feedback to Methyl-donor Homeostasis

This study identifies the GNMT N-terminal tail and its phosphorylation at S9 as a regulatory mechanism linking folate feedback to SAM homeostasis.

Productive mRNA Chromatin Escape is Promoted by PRMT5 Methylation of SNRPB

The paper shows PRMT5 promotes chromatin escape of mRNAs by methylating SNRPB, affecting splicing and nuclear export.

PRMT5 activity sustains histone production to maintain genome integrity

This study shows PRMT5 sustains histone transcription and protein synthesis during S phase, maintaining genome integrity by regulating histone H4 methylation.

Loss of CARM1 alters the developmental programming of Glioma stem-like cells and creates a druggable NGFR/NTRK dependency

This study shows that CARM1 loss in GSCs disrupts developmental programming, shifts lineage towards radial glia, and creates a dependency on NGFR/NTRK signaling, making them vulnerable to NTRK inhibitors.

TTLL4 glutamyltransferase is a therapeutic target for NPM1-mutated acute myeloid leukemia

This study identifies TTLL4 as a therapeutic target in NPM1-mutated AML by showing its role in stabilizing NPM1c and promoting differentiation block, with a small molecule inhibitor demonstrating efficacy.

EXOSC4 is recruited by histone H3 co-modified with K9me3 and acetylations to surveil non-coding transcription

The paper identifies EXOSC4's interaction with a specific histone modification pair and shows its role in regulating non-coding transcription.

PRMT5 is required for full-length HTT expression by repressing multiple proximal intronic polyadenylation sites

This paper identifies PRMT5 as a regulator of HTT mRNA splicing and alternative polyadenylation, showing that its inhibition reduces full-length HTT protein levels by promoting premature termination and cleavage.

Broad de-regulated U2AF1 splicing is prognostic and augments leukemic transformation via protein arginine methyltransferase activation

The paper identifies a splicing mechanism in AML independent of mutations, showing it drives poor prognosis and can be targeted with PRMT5 inhibition.

Histone H2A serine-1 phosphorylation is a chaperone-dependent signal for dimerization with H2B and for enhanced deposition

The paper shows H2A serine-1 phosphorylation is required for H2A-H2B dimer incorporation into chromatin and is regulated by Npm2 and H2B.

Transcriptomic and proteomic regulation through abundant, dynamic, and independent arginine methylation by Type I and Type II PRMTs

The paper investigates the substrate preferences and functional consequences of Type I and II PRMTs by inhibiting them in A549 cells and analyzing proteomic and transcriptomic changes.