Mechanical determinants of chromatin topology and gene expression

Jha, Rajiv Kumar; Levens, David; Kouzine, Fedor

doi:10.1080/19491034.2022.2038868

Cited by 26 publications

(23 citation statements)

References 146 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…suggest that the concerted action of NIPBL and DIVACs increases the rate of transcription initiation of genes within the TADs, but also promotes RNA polymerase II to stall more frequently ( 73 , 76 ). The parallels between the actions of FIS and NIPBL suggest that the DIVAC enhancer-binding proteins may help the TADs become negatively supercoiled ( 77 , 78 ) which helps binding of transcription factors that create pre-initiation complex ( 79 , 80 ) or promotes the formation of DNA structures such as R-loops favored by AID ( 31 , 32 , 37 , 81–83 ).…”

Section: Discussionmentioning

confidence: 99%

Human activation-induced deaminase lacks strong replicative strand bias or preference for cytosines in hairpin loops

Sakhtemani

Perera

Hübschmann

et al. 2022

Nucleic Acids Research

View full text Add to dashboard Cite

Activation-induced deaminase (AID) is a DNA-cytosine deaminase that mediates maturation of antibodies through somatic hypermutation and class-switch recombination. While it causes mutations in immunoglobulin heavy and light chain genes and strand breaks in the switch regions of the immunoglobulin heavy chain gene, it largely avoids causing such damage in the rest of the genome. To help understand targeting by human AID, we expressed it in repair-deficient Escherichia coli and mapped the created uracils in the genomic DNA using uracil pull-down and sequencing, UPD-seq. We found that both AID and the human APOBEC3A preferentially target tRNA genes and transcription start sites, but do not show preference for highly transcribed genes. Unlike A3A, AID did not show a strong replicative strand bias or a preference for hairpin loops. Overlapping uracilation peaks between these enzymes contained binding sites for a protein, FIS, that helps create topological domains in the E. coli genome. To confirm whether these findings were relevant to B cells, we examined mutations from lymphoma and leukemia genomes within AID-preferred sequences. These mutations also lacked replicative strand bias or a hairpin loop preference. We propose here a model for how AID avoids causing mutations in the single-stranded DNA found within replication forks.

show abstract

Section: Discussionmentioning

confidence: 99%

Human activation-induced deaminase lacks strong replicative strand bias or preference for cytosines in hairpin loops

Sakhtemani

Perera

Hübschmann

et al. 2022

Nucleic Acids Research

View full text Add to dashboard Cite

show abstract

“…This information is considered a cellular memory that is transmitted from the parent cells to the daughters by mitosis. The status of DNA 3D structure controls transcription and gene expression [70]. It has been recorded that parent cells with excess supercoiling deliver daughter cells with the impaired cell cycle.…”

Section: Epigenetic Therapy and Cancer Colonmentioning

confidence: 99%

Perspective Chapter: Topoisomerase 1 and Colo Rectal Carcinoma

Helaly¹,

Ghorab²

2023

DNA Replication - Epigenetic Mechanisms and Gene Therapy Applications

View full text Add to dashboard Cite

Topoisomerase 1 is the main enzyme playing an important role in relaxing. The supercoiled DNA strands allow the replication fork to transcribe the DNA to RNA and finally control protein production in active and replicating cells. Blocking this essential machinery is a cornerstone mechanism in treating tumors, such as liver, breast, and metastatic colorectal carcinoma. Irinotecan is a topoisomerase inhibitor that blocks the replication ending in DNA break and tumor cell death. This chemotherapy has been successfully used in combination to overcome metastatic colorectal carcinoma. The topoisomerase-1 inhibitor makes a protein DNA complex stuck with the replicating fork creating a single DNA break, unlike topoisomerase-2, which is responsible for double DNA break. This inhibitor is exposed to drug resistance with complex machinery. Drug resistance can occur as a result of altered DNA methylation, changes in topoisomerase expression, histone recombination, or drug export pump. High expression of topoisomerase-1 is a marker of the number of tumors suggesting multiple roles of topoisomerase-1.

show abstract

“…Topoisomerases associate with the transcribing Pol II and change the topology and folding of DNA. Jha et al [ 57 ] proposed that transcription-driven positive supercoiling could compact DNA and decrease the distance between enhancer and promoter. Furthermore, several transcription factors were shown to bind more efficiently to DNA when the binding sequence was in the context of negative supercoils, which accumulate behind the transcribing polymerase [ 58 ].…”

Section: The Role Of Enhancer Transcription and Ernamentioning

confidence: 99%

Enhancer-Mediated Formation of Nuclear Transcription Initiation Domains

Gibbons

Fang

Spicola

et al. 2022

IJMS

View full text Add to dashboard Cite

Enhancers in higher eukaryotes and upstream activating sequences (UASs) in yeast have been shown to recruit components of the RNA polymerase II (Pol II) transcription machinery. At least a fraction of Pol II recruited to enhancers in higher eukaryotes initiates transcription and generates enhancer RNA (eRNA). In contrast, UASs in yeast do not recruit transcription factor TFIIH, which is required for transcription initiation. For both yeast and mammalian systems, it was shown that Pol II is transferred from enhancers/UASs to promoters. We propose that there are two modes of Pol II recruitment to enhancers in higher eukaryotes. Pol II complexes that generate eRNAs are recruited via TFIID, similar to mechanisms operating at promoters. This may involve the binding of TFIID to acetylated nucleosomes flanking the enhancer. The resulting eRNA, together with enhancer-bound transcription factors and co-regulators, contributes to the second mode of Pol II recruitment through the formation of a transcription initiation domain. Transient contacts with target genes, governed by proteins and RNA, lead to the transfer of Pol II from enhancers to TFIID-bound promoters.

show abstract

Mechanical determinants of chromatin topology and gene expression

Cited by 26 publications

References 146 publications

Human activation-induced deaminase lacks strong replicative strand bias or preference for cytosines in hairpin loops

Human activation-induced deaminase lacks strong replicative strand bias or preference for cytosines in hairpin loops

Perspective Chapter: Topoisomerase 1 and Colo Rectal Carcinoma

Enhancer-Mediated Formation of Nuclear Transcription Initiation Domains

Contact Info

Product

Resources

About