A Read/Write Mechanism Connects p300 Bromodomain Function to H2A.Z Acetylation

Colino‐Sanguino, Yolanda; Cornett, Evan M.; Moulder, David; Smith, Grady C.; Hrit, Joel; Cordeiro-Spinetti, Eric; Vaughan, Robert M.; Krajewski, Krzysztof; Rothbart, Scott B.; Clark, Susan J.; Valdés-Mora, Fátima

doi:10.1016/j.isci.2019.10.053

Cited by 18 publications

(19 citation statements)

References 72 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Interestingly, a significant portion of this acetylation occurs as diacetylation and triacetylation of K4, K7, and K11. TIP60 [68,84], p300 [73], and KAT2A [85], in the context of DNA repair, can acetylate H2A.Z in cells. Bromodomain proteins bind to acetylated lysines and in vitro studies showed that the bromodomain PHD finger transcription factor (BPTF) interacts with K7ac on H2A.Z.2, while the bromodomain of CECR2 preferentially binds H2A.Z.1ac [142]; however, further in vivo validation will be necessary to confirm this interaction.…”

Section: Glossarymentioning

confidence: 99%

“…Interestingly, various studies have found that active intragenic enhancers in expressed genes are depleted of H2A.Z or H2A.Zac [73,74], which could be due to active removal of H2A.Z at gene bodies during transcription elongation [75,76]. Notably H2A.Z-marked active enhancers may not be present within the gene they activate, as transcription elongation of the gene would remove H2A.Z from the enhancer, suggesting that H2A.Z enhancers may likely be acting as trans-regulatory elements.…”

Section: Trends Trends In In Genetics Geneticsmentioning

confidence: 99%

“…Tip60 creates a hyperacetylated local chromatin that spreads away from the DSBs to enable the formation of an open chromatin region at DSBs [82,83]. Even though it has been shown that Tip60 regulates H2A.Z acetylation [58,73,84], a direct acetylation activity towards H2A.Z has not been yet reported in the context of DNA repair. By contrast, KAT2A was shown to acetylate H2A.Z.1, but not H2A.Z.2, at promoters through interaction with a DNA repair complex that surveys transcription to repair DNA lesions that potentially impact transcription fidelity [85].…”

Section: Role In Dna Repairmentioning

confidence: 99%

See 2 more Smart Citations

The H2A.Z-nucleosome code in mammals: emerging functions

2022

Self Cite

View full text Add to dashboard Cite

H2A.Z is a histone variant that provides specific structural and docking-side properties to the nucleosome, resulting in diverse and specialised molecular and cellular functions. In this review, we discuss the latest studies uncovering new functional aspects of mammalian H2A.Z in gene transcription, including pausing and elongation of RNA polymerase II (RNAPII) and enhancer activity; DNA repair; DNA replication; and 3D chromatin structure. We also review the recently described role of H2A.Z in embryonic development, cell differentiation, neurodevelopment, and brain function. In conclusion, our cumulative knowledge of H2A.Z over the past 40 years, in combination with the implementation of novel molecular technologies, is unravelling an unexpected and complex role of histone variants in gene regulation and disease.

show abstract

Section: Glossarymentioning

confidence: 99%

Section: Trends Trends In In Genetics Geneticsmentioning

confidence: 99%

Section: Role In Dna Repairmentioning

confidence: 99%

See 1 more Smart Citation

The H2A.Z-nucleosome code in mammals: emerging functions

2022

Self Cite

View full text Add to dashboard Cite

show abstract

“…Hence, differential acetylation of the two isoforms could alter their different functional outcome. For instance, the flexibility of the n-terminal tail between different isoforms can be enhanced by their specific acetylation, regardless of the lack of difference observed in the acetylation rate of H2A.Z-1 and H2A.Z-2 by p300 [95]. Also, it has been shown that H2A.Z-2 preferentially associates with H3K4me3 [18].…”

Section: Discussionmentioning

confidence: 99%

Deciphering the Enigma of the Histone H2A.Z-1/H2A.Z-2 Isoforms: Novel Insights and Remaining Questions

Cheema

Good

Kim

et al. 2020

Cells

View full text Add to dashboard Cite

The replication independent (RI) histone H2A.Z is one of the more extensively studied variant members of the core histone H2A family, which consists of many replication dependent (RD) members. The protein has been shown to be indispensable for survival, and involved in multiple roles from DNA damage to chromosome segregation, replication, and transcription. However, its functional involvement in gene expression is controversial. Moreover, the variant in several groups of metazoan organisms consists of two main isoforms (H2A.Z-1 and H2A.Z-2) that differ in a few (3–6) amino acids. They comprise the main topic of this review, starting from the events that led to their identification, what is currently known about them, followed by further experimental, structural, and functional insight into their roles. Despite their structural differences, a direct correlation to their functional variability remains enigmatic. As all of this is being elucidated, it appears that a strong functional involvement of isoform variability may be connected to development.

show abstract

“…In this study, we developed a novel dipyrene analogue, Pyr-A, and used it to probe biomolecule condensates formed by LLPS. These include in vitro droplets formed by intrinsically disordered regions (IDRs) of bromodomain-containing protein 4 (BRD4) ( Caputo et al., 2021 ; Colino-Sanguino et al., 2019 ; Sabari et al., 2018 ), and centrosomes, which are dynamic and spherical membraneless intracellular organelles ( Tiwary and Zheng, 2019 ) ( Figure 1 B). Centrosomes are surrounded by pericentriolar material (PCM) ( Andersen et al., 2003 ).…”

Section: Introductionmentioning

confidence: 99%

A light-switching pyrene probe to detect phase-separated biomolecules

et al. 2021

View full text Add to dashboard Cite

Summary Biomolecules may undergo liquid–liquid phase separation (LLPS) to spatiotemporally compartmentalize and regulate diverse biological processes. Because the number of tools to directly probe LLPS is limited (ie. FRAP, FRET, fluorescence microscopy, fluorescence anisotropy, circular dichroism, etc.), the physicochemical traits of phase-separated condensates remain largely elusive. Here, we introduce a light-switching dipyrene probe (Pyr-A) that forms monomers in either hydrophobic or viscous environments, and intramolecular excimers in aqueous solutions. By exploiting their distinct fluorescence emission spectra, we used fluorescent microscopic imaging to study phase-separated condensates formed by in vitro protein droplets and membraneless intracellular organelles (centrosomes). Ratiometric measurement of excimer and monomer fluorescence intensities showed that protein droplets became hydrophobic and viscous as their size increased. Moreover, centrosomes became hydrophobic and viscous during maturation. Our results show that Pyr-A is a valuable tool to characterize LLPS and enhance our understanding of phase separation underlying biological functions.

show abstract

A Read/Write Mechanism Connects p300 Bromodomain Function to H2A.Z Acetylation

Abstract: HIGHLIGHTS p300 acetylates H2A.Z at multiple N-terminal lysine residues Interaction of p300 bromodomain with H4ac enhances H2A.Zac H2A.Zac and H4ac colocalize at active regulatory regions H4ac and H2A.Zac differential signature can define the enhancer state

Cited by 18 publications

References 72 publications

The H2A.Z-nucleosome code in mammals: emerging functions

The H2A.Z-nucleosome code in mammals: emerging functions

Deciphering the Enigma of the Histone H2A.Z-1/H2A.Z-2 Isoforms: Novel Insights and Remaining Questions

A light-switching pyrene probe to detect phase-separated biomolecules

Contact Info

Product

Resources

About