Humans

The concurrence of DNA methylation and demethylation is associated with transcription regulation

The mammalian DNA methylome is formed by two antagonizing processes, methylation by DNA methyltransferases (DNMT) and demethylation by ten-eleven translocation (TET) dioxygenases. Although the dynamics of either methylation or demethylation have been …

Statistical Assessment of Depth Normalization for Small RNA Sequencing

PURPOSE: Methods for depth normalization have been assessed primarily with simulated data or cell-line-mixture data. There is a pressing need for benchmark data enabling a more realistic and objective assessment, especially in the context of small …

Cystine transporter regulation of pentose phosphate pathway dependency and disulfide stress exposes a targetable metabolic vulnerability in cancer

SLC7A11-mediated cystine uptake is critical for maintaining redox balance and cell survival. Here we show that this comes at a significant cost for cancer cells with high levels of SLC7A11. Actively importing cystine is potentially toxic due to its …

Neurofibromin Is an Estrogen Receptor-α Transcriptional Co-repressor in Breast Cancer

We report that neurofibromin, a tumor suppressor and Ras-GAP (GTPase-activating protein), is also an estrogen receptor-α (ER) transcriptional co-repressor through leucine/isoleucine-rich motifs that are functionally independent of GAP activity. GAP …

A PARP1-BRG1-SIRT1 axis promotes HR repair by reducing nucleosome density at DNA damage sites

Creating access to DNA double-strand break (DSB) sites in the chromatin context is an essential step during the repair process, but much remains to be determined about its regulatory mechanisms. Here, using a novel reporter cassette for simultaneous …

Histone H3.3 G34 Mutations Alter Histone H3K36 and H3K27 Methylation In Cis

Histone H3 encoding genes, particularly H3F3A and H3F3B, the genes encoding the variant histone H3.3, are mutated at high frequency in pediatric brain and bone malignancies. Compared to the extensive studies on K27M and K36M mutations, little is …

Recognition of histone acetylation by the GAS41 YEATS domain promotes H2A.Z deposition in non-small cell lung cancer

Histone acetylation is associated with active transcription in eukaryotic cells. It helps to open up the chromatin by neutralizing the positive charge of histone lysine residues and providing binding platforms for \"reader\" proteins. The bromodomain …

Acetylation on histone H3 lysine 9 mediates a switch from transcription initiation to elongation

The transition from transcription initiation to elongation is a key regulatory step in gene expression, which requires RNA polymerase II (pol II) to escape promoter proximal pausing on chromatin. Although elongation factors promote pause release …

The glutamate/cystine antiporter SLC7A11/xCT enhances cancer cell dependency on glucose by exporting glutamate

Cancer cells with specific genetic alterations may be highly dependent on certain nutrients for survival, which can inform therapeutic strategies to target these cancer-specific metabolic vulnerabilities. The glutamate/cystine antiporter solute …

Chromatin remodeling during the in vivo glial differentiation in early Drosophila embryos

Chromatin remodeling plays a critical role in gene regulation and impacts many biological processes. However, little is known about the relationship between chromatin remodeling dynamics and in vivo cell lineage commitment. Here, we reveal the …