DNA Oxidation as Triggered by H3K9me2 Demethylation Drives Estrogen-Induced Gene Expression

  title={DNA Oxidation as Triggered by H3K9me2 Demethylation Drives Estrogen-Induced Gene Expression},
  author={Bruno Perillo and Maria Neve Ombra and Alessandra Bertoni and Concetta Cuozzo and Silvana Sacchetti and Anna Sasso and Lorenzo Chiariotti and Antonio Malorni and Ciro Abbondanza and Enrico Avvedimento},
  pages={202 - 206}
Modifications at the N-terminal tails of nucleosomal histones are required for efficient transcription in vivo. We analyzed how H3 histone methylation and demethylation control expression of estrogen-responsive genes and show that a DNA-bound estrogen receptor directs transcription by participating in bending chromatin to contact the RNA polymerase II recruited to the promoter. This process is driven by receptor-targeted demethylation of H3 lysine 9 at both enhancer and promoter sites and is… 

Analysis of histone posttranslational modifications in the control of chromatin plasticity observed at estrogen-responsive sites in human breast cancer cells.

It is well established that histone posttranslational modifications mediate the control of gene expression played by chromatin and many alternatives are open to drive transcription of inducible genes.

LSD1-mediated demethylation of histone H3 lysine 4 triggers Myc-induced transcription

The role of transient LSD1-mediated demethylation of H3K4 leading to local DNA oxidation as driving force in the assembly of the Myc-induced transcription initiation complex is highlighted.

Mechanism of retinoic acid-induced transcription: histone code, DNA oxidation and formation of chromatin loops

These data mechanistically link chromatin loops, histone methylation changes and localized DNA repair with transcription.

Nuclear receptor-induced transcription is driven by spatially and timely restricted waves of ROS

Members of the family of nuclear receptors prevent the potential damage to DNA during transcription of target genes elicited by the use of ROS to shape chromatin using phosphorylated serine 10 in histone H3 to prevent unbalanced DNA oxidation waves.

Cytosine hydroxymethylation by TET enzymes: From the control of gene expression to the regulation of DNA repair mechanisms, and back

The role of the regulation of the 5-mC/5-hmC balance by TET enzymes in the context of transcription modulation as well as DNA repair processes is reviewed and the potential involvement of TET proteins in DNA repair mechanisms associated with transcription activation is speculated on.

Mechanism of retinoic acid-induced transcription: histone code, DNA oxidation and formation of chromatin loops

These data mechanistically link chromatin loops, histone methylation changes and localized DNA repair with transcription in eukaryotes.

DNA excision repair proteins and Gadd45 as molecular players for active DNA demethylation

Functional and evolutionary implications of mechanisms underlying active DNA demethylation, including non-enzymatic Gadd45 proteins, which function to recruit enzymatic machineries and promote coupling of deamination, base and nucleotide-excision repair in the process of DNA dem methylation are discussed.

Base excision repair facilitates a functional relationship between Guanine oxidation and histone demethylation.

Current studies suggesting a role for BER proteins in transcriptional regulation of gene expression via BER-coupled active DNA demethylation in mammalian cells could broaden cancer therapeutic strategies to include epigenetic modifiers combined with BER inhibitors.

Ligand-induced gene activation is associated with oxidative genome damage whose repair is required for transcription

The formation of genomic oxidized bases and single-strand breaks during ligand-induced gene activation via histone/CpG demethylation is documents and suggests that the extent of oxidative genome damage resulting from various cellular processes is substantially underestimated.

DNA oxidation drives Myc mediated transcription

A model that links histone H3 methylation code to Myc target genes is proposed, which seems to modulate at least two crucial steps in transcription, i.e. chromatin modifications for initiation and RNAPII pause release for productive elongation.



A Topoisomerase IIß-Mediated dsDNA Break Required for Regulated Transcription

It is reported that the signal-dependent activation of gene transcription by nuclear receptors and other classes of DNA binding transcription factors, including activating protein 1, requires DNA topoisomerase IIβ-dependent, transient, site-specific dsDNA break formation.

LSD1 demethylates repressive histone marks to promote androgen-receptor-dependent transcription

It is shown that lysine-specific demethylase 1 co-localizes with the androgen receptor in normal human prostate and prostate tumour and pargyline is identified as an inhibitor of LSD1, providing a mechanism by which demethylases control specific gene expression.

Functional and physical interaction between the histone methyl transferase Suv39H1 and histone deacetylases.

The results suggest that a complex containing both the Suv39H1 histone methyl transferase and histone deacetylases could be involved in heterochromatin silencing or transcriptional repression by Rb.

Translating the Histone Code

It is proposed that this epigenetic marking system represents a fundamental regulatory mechanism that has an impact on most, if not all, chromatin-templated processes, with far-reaching consequences for cell fate decisions and both normal and pathological development.

A role for the CPF 3'-end processing machinery in RNAP II-dependent gene looping.

A model for RNAP II transcription is proposed in which promoter and terminator regions are juxtaposed, and that the resulting gene loops facilitate transcription reinitiation by the same molecule ofRNAP II in a manner dependent upon Ssu72-mediated CTD dephosphorylation.

The catalytic subunit of the proteasome is engaged in the entire process of estrogen receptor‐regulated transcription

It is demonstrated that the recruitment of LMP2 by SRC coactivators is necessary for cyclic association of ER‐regulated transcription complexes on ER targets, and a mechanism by which the proteasome machinery is recruited in ER‐mediated gene transcription is revealed.