Co-condensation between transcription factor and coactivator p300 modulates transcriptional bursting kinetics

Ma, Liang; Gao, Ze-Yue; Wu, Jiegen; Zhong, Bijunyao; Xie, Yuchen; Huang, Wen Liang; Lin, Yihan

doi:10.1016/j.molcel.2021.01.031

Cited by 110 publications

(114 citation statements)

References 77 publications

Supporting

Mentioning

102

Contrasting

Order By: Relevance

“…Functional consequences of these acetylation events on the recipient proteins almost certainly occur and will require a major experimental effort to be fully deciphered. CBP/p300 co-condenses with transcription factors and could have a role in the transcriptional bursting of genes with the broad epigenetic domain [ 60 ].…”

Section: Chromatin Dynamics Of Broad Epigenetic Domainsmentioning

confidence: 99%

“…5 ). Transcription factors also recruit chromatin modifying enzymes [protein arginine methyltransferase 1 (PRMT1), CBP/300] to enhancers/super-enhancers and promoters [ 51 , 60 , 103 – 105 ]. PRMT1 is required to establish the active chromatin state and is needed for hematopoietic differentiation in avian and mammalian cells [ 103 , 105 , 106 ].…”

Section: A Model For the Establishment Of The Broad Epigenetic Domainmentioning

confidence: 99%

“…Interaction between the locus control region (a super-enhancer) and the β-globin promoter in the β-globin gene (broad epigenetic domain) is prevented when PRMT1 was knocked down. The interaction of the locus control region with the globin promoter increases transcriptional bursting (burst fraction and size) [ 60 ].…”

Section: A Model For the Establishment Of The Broad Epigenetic Domainmentioning

confidence: 99%

“…However, the enzyme’s role in creating chromatin accessibility at enhancers/super-enhancers does not require the enzyme’s catalytic activity, which produces H3K4me1 [ 108 , 109 ]. A model is emerging in which interactions (multivalent/hydrophobic) between the intrinsic disordered domains of Mediator (e.g., MED1 subunit), CBP/p300, and transcription factors form phase-separated condensates [ 60 , 102 , 110 ] (Fig. 5 ).…”

Section: A Model For the Establishment Of The Broad Epigenetic Domainmentioning

confidence: 99%

See 3 more Smart Citations

The dynamic broad epigenetic (H3K4me3, H3K27ac) domain as a mark of essential genes

et al. 2021

View full text Add to dashboard Cite

Transcriptionally active chromatin is marked by tri-methylation of histone H3 at lysine 4 (H3K4me3) located after first exons and around transcription start sites. This epigenetic mark is typically restricted to narrow regions at the 5`end of the gene body, though a small subset of genes have a broad H3K4me3 domain which extensively covers the coding region. Although most studies focus on the H3K4me3 mark, the broad H3K4me3 domain is associated with a plethora of histone modifications (e.g., H3 acetylated at K27) and is therein termed broad epigenetic domain. Genes marked with the broad epigenetic domain are involved in cell identity and essential cell functions and have clinical potential as biomarkers for patient stratification. Reducing expression of genes with the broad epigenetic domain may increase the metastatic potential of cancer cells. Enhancers and super-enhancers interact with the broad epigenetic domain marked genes forming a hub of interactions involving nucleosome-depleted regions. Together, the regulatory elements coalesce with transcription factors, chromatin modifying/remodeling enzymes, coactivators, and the Mediator and/or Integrator complex into a transcription factory which may be analogous to a liquid–liquid phase-separated condensate. The broad epigenetic domain has a dynamic chromatin structure which supports frequent transcription bursts. In this review, we present the current knowledge of broad epigenetic domains.

show abstract

Section: Chromatin Dynamics Of Broad Epigenetic Domainsmentioning

confidence: 99%

Section: A Model For the Establishment Of The Broad Epigenetic Domainmentioning

confidence: 99%

Section: A Model For the Establishment Of The Broad Epigenetic Domainmentioning

confidence: 99%

Section: A Model For the Establishment Of The Broad Epigenetic Domainmentioning

confidence: 99%

See 2 more Smart Citations

The dynamic broad epigenetic (H3K4me3, H3K27ac) domain as a mark of essential genes

et al. 2021

View full text Add to dashboard Cite

show abstract

“…A link between super-enhancers (SEs) and cocondensates was illustrated by findings that SE-enriched transcriptional coactivators BRD4 and MED1 form nuclear puncta at SEs that exhibit properties of liquid-like condensates to compartmentalize and concentrate transcription apparatus from nuclear extracts (Sabari, 2018). Intrinsically disordered regions (IDRs) of HAT transcription coactivator p300 interact with TF-transactivation domains (TADs), forming cocondensates that promote p300 transactivation and stabilize TF-p300 assembly, priming the recruitment of coactivator BRD4, and contribute to transcriptional bursting regulation and cooperative gene control (Ma, 2021). However, histone acetylation by p300 also antagonizes chromatin phase separation, while BRD4 helps highly acetylated chromatin to form a new phase-separated state with droplets of distinct physical properties (Gibson et al, 2019).…”

Section: Bromodomain and Extra-terminal Domain Proteins In Condensate Formationmentioning

confidence: 99%

The Functions of BET Proteins in Gene Transcription of Biology and Diseases

Cheung

Kim

Zhou

2021

Front. Mol. Biosci.

View full text Add to dashboard Cite

The BET (bromodomain and extra-terminal domain) family proteins, consisting of BRD2, BRD3, BRD4, and testis-specific BRDT, are widely acknowledged as major transcriptional regulators in biology. They are characterized by two tandem bromodomains (BDs) that bind to lysine-acetylated histones and transcription factors, recruit transcription factors and coactivators to target gene sites, and activate RNA polymerase II machinery for transcriptional elongation. Pharmacological inhibition of BET proteins with BD inhibitors has been shown as a promising therapeutic strategy for the treatment of many human diseases including cancer and inflammatory disorders. The recent advances in bromodomain protein biology have further uncovered the complex and versatile functions of BET proteins in the regulation of gene expression in chromatin. In this review article, we highlight our current understanding of BET proteins’ functions in mediating protein–protein interactions required for chromatin-templated gene transcription and splicing, chromatin remodeling, DNA replication, and DNA damage repair. We further discuss context-dependent activator vs. repressor functions of individual BET proteins, isoforms, and bromodomains that may be harnessed for future development of BET bromodomain inhibitors as emerging epigenetic therapies for cancer and inflammatory disorders.

show abstract

May the force be with you: Nuclear condensates function beyond transcription control

et al. 2023

View full text Add to dashboard Cite

Over the past decade, research has revealed biomolecular condensates' relevance in diverse cellular functions. Through a phase separation process, they concentrate macromolecules in subcompartments shaping the cellular organization and physiology. In the nucleus, biomolecular condensates assemble relevant biomolecules that orchestrate gene expression. We here hypothesize that chromatin condensates can also modulate the nongenetic functions of the genome, including the nuclear mechanical properties. The importance of chromatin condensates is supported by the genetic evidence indicating that mutations in their members are causative of a group of rare Mendelian diseases named chromatinopathies (CPs). Despite a broad spectrum of clinical features and the perturbations of the epigenetic machinery characterizing the CPs, recent findings highlighted negligible changes in gene expression. These data argue in favor of possible noncanonical functions of chromatin condensates in regulating the genome's spatial organization and, consequently, the nuclear mechanics. In this review, we discuss how condensates may impact nuclear mechanical properties, thus affecting the cellular response to mechanical cues and, eventually, cell fate and identity.Chromatin condensates organize macromolecules in the nucleus orchestrating the transcription regulation and mutations in their members are responsible for rare diseases named chromatinopathies. We argue that chromatin condensates, in concert with the nuclear lamina, may also govern the nuclear mechanical properties affecting the cellular response to external cues.

show abstract

Co-condensation between transcription factor and coactivator p300 modulates transcriptional bursting kinetics

Cited by 110 publications

References 77 publications

The dynamic broad epigenetic (H3K4me3, H3K27ac) domain as a mark of essential genes

The dynamic broad epigenetic (H3K4me3, H3K27ac) domain as a mark of essential genes

The Functions of BET Proteins in Gene Transcription of Biology and Diseases

May the force be with you: Nuclear condensates function beyond transcription control

Contact Info

Product

Resources

About