scholarly journals Pre-marked chromatin and transcription factor co-binding shape the pioneering activity of Foxa2

2019 ◽  
Author(s):  
Filippo M. Cernilogar ◽  
Stefan Hasenöder ◽  
Zeyang Wang ◽  
Katharina Scheibner ◽  
Ingo Burtscher ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Binding Sites ◽  
Specific Binding ◽  
Embryonic Stem ◽  
Chromatin Accessibility ◽  
Specific Binding Sites ◽  
Nucleosomal Dna ◽  
Cell Type Specific ◽  
Chromatin Opening ◽  
Selection Of

AbstractPioneer transcription factors (PTF) can recognize their binding sites on nucleosomal DNA and trigger chromatin opening for recruitment of other non-pioneer transcription factors. However, critical properties of PTFs are still poorly understood, such as how these transcription factors selectively recognize cell type-specific binding sites and under which conditions can they can initiate chromatin remodelling. Here we show that early endoderm binding sites of the paradigm PTF Foxa2 are epigenetically primed by low levels of active chromatin modifications in embryonic stem cells (ESC). Priming of these binding sites is supported by preferential recruitment of Foxa2 to endoderm binding sites compared to lineage-inappropriate binding sites, when ectopically expressed in ESCs. We further show that binding of Foxa2 is required for chromatin opening during endoderm differentiation. However, increased chromatin accessibility was only detected on binding sites which are synergistically bound with other endoderm transcription factors. Thus, our data suggest that binding site selection of PTFs is directed by the chromatin environment and that chromatin opening requires collaboration of PTFs with additional transcription factors.

scholarly journals Pre-marked chromatin and transcription factor co-binding shape the pioneering activity of Foxa2

2019 ◽  
Vol 47 (17) ◽  
pp. 9069-9086 ◽  
Author(s):  
Filippo M Cernilogar ◽  
Stefan Hasenöder ◽  
Zeyang Wang ◽  
Katharina Scheibner ◽  
Ingo Burtscher ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Binding Sites ◽  
Specific Binding ◽  
Embryonic Stem ◽  
Chromatin Accessibility ◽  
Specific Binding Sites ◽  
Nucleosomal Dna ◽  
Cell Type Specific ◽  
Chromatin Opening ◽  
Selection Of

Abstract Pioneer transcription factors (PTF) can recognize their binding sites on nucleosomal DNA and trigger chromatin opening for recruitment of other non-pioneer transcription factors. However, critical properties of PTFs are still poorly understood, such as how these transcription factors selectively recognize cell type-specific binding sites and under which conditions they can initiate chromatin remodelling. Here we show that early endoderm binding sites of the paradigm PTF Foxa2 are epigenetically primed by low levels of active chromatin modifications in embryonic stem cells (ESC). Priming of these binding sites is supported by preferential recruitment of Foxa2 to endoderm binding sites compared to lineage-inappropriate binding sites, when ectopically expressed in ESCs. We further show that binding of Foxa2 is required for chromatin opening during endoderm differentiation. However, increased chromatin accessibility was only detected on binding sites which are synergistically bound with other endoderm transcription factors. Thus, our data suggest that binding site selection of PTFs is directed by the chromatin environment and that chromatin opening requires collaboration of PTFs with additional transcription factors.

scholarly journals Holocentromeres are dispersed point centromeres localized at transcription factor hotspots

eLife ◽  
2014 ◽  
Vol 3 ◽  
Author(s):  
Florian A Steiner ◽  
Steven Henikoff
Keyword(s):  
Transcription Factor ◽  
Transcription Factors ◽  
Caenorhabditis Elegans ◽  
Binding Sites ◽  
Specific Binding ◽  
Basic Unit ◽  
Centromeric Chromatin ◽  
Sequence Composition ◽  
Specific Binding Sites ◽  
Mechanistic Basis

Centromeres vary greatly in size and sequence composition, ranging from ‘point’ centromeres with a single cenH3-containing nucleosome to ‘regional’ centromeres embedded in tandemly repeated sequences to holocentromeres that extend along the length of entire chromosomes. Point centromeres are defined by sequence, whereas regional and holocentromeres are epigenetically defined by the location of cenH3-containing nucleosomes. In this study, we show that Caenorhabditis elegans holocentromeres are organized as dispersed but discretely localized point centromeres, each forming a single cenH3-containing nucleosome. These centromeric sites co-localize with kinetochore components, and their occupancy is dependent on the cenH3 loading machinery. These sites coincide with non-specific binding sites for multiple transcription factors (‘HOT’ sites), which become occupied when cenH3 is lost. Our results show that the point centromere is the basic unit of holocentric organization in support of the classical polycentric model for holocentromeres, and provide a mechanistic basis for understanding how centromeric chromatin might be maintained.

scholarly journals Binding of disparate transcriptional activators to nucleosomal DNA is inherently cooperative.

1995 ◽  
Vol 15 (3) ◽  
pp. 1405-1421 ◽  
Author(s):  
C C Adams ◽  
J L Workman
Keyword(s):  
Transcription Factors ◽  
Dna Binding ◽  
Binding Sites ◽  
Specific Binding ◽  
General Mechanism ◽  
Nf Kappa B ◽  
Nucleosomal Dna ◽  
Nucleosome Binding

To investigate mechanisms by which multiple transcription factors access complex promoters and enhancers within cellular chromatin, we have analyzed the binding of disparate factors to nucleosome cores. We used a purified in vitro system to analyze binding of four activator proteins, two GAL4 derivatives, USF, and NF-kappa B (KBF1), to reconstituted nucleosome cores containing different combinations of binding sites. Here we show that binding of any two or all three of these factors to nucleosomal DNA is inherently cooperative. Thus, the binuclear Zn clusters of GAL4, the helix-loop-helix/basic domains of USF, and the rel domain of NF-kappa B all participated in cooperative nucleosome binding, illustrating that this effect is not restricted to a particular DNA-binding domain. Simultaneous binding by two factors increased the affinity of individual factors for nucleosomal DNA by up to 2 orders of magnitude. Importantly, cooperative binding resulted in efficient nucleosome binding by factors (USF and NF-kappa B) which independently possess little nucleosome-binding ability. The participation of GAL4 derivatives in cooperative nucleosome binding required only DNA-binding and dimerization domains, indicating that disruption of histone-DNA contacts by factor binding was responsible for the increased affinity of additional factors. Cooperative nucleosome binding required sequence-specific binding of all transcription factors, appeared to have spatial constraints, and was independent of the orientation of the binding sites on the nucleosome. These results indicate that cooperative nucleosome binding is a general mechanism that may play a significant role in loading complex enhancer and promoter elements with multiple diverse factors in chromatin and contribute to the generation of threshold responses and transcriptional synergy by multiple activator sites in vivo.

scholarly journals How do transcription factors select specific binding sites in the genome?

2009 ◽  
Vol 16 (11) ◽  
pp. 1118-1120 ◽  
Author(s):  
Yongping Pan ◽  
Chung-Jung Tsai ◽  
Buyong Ma ◽  
Ruth Nussinov
Keyword(s):  
Transcription Factors ◽  
Binding Sites ◽  
Specific Binding ◽  
Specific Binding Sites

scholarly journals High throughput screening identifies SOX2 as a super pioneer factor that inhibits DNA methylation maintenance at its binding sites

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Ludovica Vanzan ◽  
Hadrien Soldati ◽  
Victor Ythier ◽  
Santosh Anand ◽  
Simon M. G. Braun ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Transcription Factors ◽  
Binding Sites ◽  
High Throughput Screening ◽  
Methylation Status ◽  
Chromatin Accessibility ◽  
Dna Demethylation ◽  
Active Dna Demethylation ◽  
Nucleosomal Dna ◽  
Select Group

AbstractBinding of mammalian transcription factors (TFs) to regulatory regions is hindered by chromatin compaction and DNA methylation of their binding sites. Nevertheless, pioneer transcription factors (PFs), a distinct class of TFs, have the ability to access nucleosomal DNA, leading to nucleosome remodelling and enhanced chromatin accessibility. Whether PFs can bind to methylated sites and induce DNA demethylation is largely unknown. Using a highly parallelized approach to investigate PF ability to bind methylated DNA and induce DNA demethylation, we show that the interdependence between DNA methylation and TF binding is more complex than previously thought, even within a select group of TFs displaying pioneering activity; while some PFs do not affect the methylation status of their binding sites, we identified PFs that can protect DNA from methylation and others that can induce DNA demethylation at methylated binding sites. We call the latter super pioneer transcription factors (SPFs), as they are seemingly able to overcome several types of repressive epigenetic marks. Finally, while most SPFs induce TET-dependent active DNA demethylation, SOX2 binding leads to passive demethylation, an activity enhanced by the co-binding of OCT4. This finding suggests that SPFs could interfere with epigenetic memory during DNA replication.

scholarly journals Promoter G-quadruplexes and transcription factors cooperate to shape the cell type-specific transcriptome

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Sara Lago ◽  
Matteo Nadai ◽  
Filippo M. Cernilogar ◽  
Maryam Kazerani ◽  
Helena Domíniguez Moreno ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Binding Sites ◽  
Specific Gene ◽  
Open Chromatin ◽  
Rna Seq ◽  
Transcript Levels ◽  
Promoter Sequences ◽  
G Quadruplex ◽  
Cell Type Specific ◽  
Folding State

AbstractCell identity is maintained by activation of cell-specific gene programs, regulated by epigenetic marks, transcription factors and chromatin organization. DNA G-quadruplex (G4)-folded regions in cells were reported to be associated with either increased or decreased transcriptional activity. By G4-ChIP-seq/RNA-seq analysis on liposarcoma cells we confirmed that G4s in promoters are invariably associated with high transcription levels in open chromatin. Comparing G4 presence, location and transcript levels in liposarcoma cells to available data on keratinocytes, we showed that the same promoter sequences of the same genes in the two cell lines had different G4-folding state: high transcript levels consistently associated with G4-folding. Transcription factors AP-1 and SP1, whose binding sites were the most significantly represented in G4-folded sequences, coimmunoprecipitated with their G4-folded promoters. Thus, G4s and their associated transcription factors cooperate to determine cell-specific transcriptional programs, making G4s to strongly emerge as new epigenetic regulators of the transcription machinery.

scholarly journals Persistent Interactions of Core Histone Tails with Nucleosomal DNA following Acetylation and Transcription Factor Binding

1998 ◽  
Vol 18 (11) ◽  
pp. 6293-6304 ◽  
Author(s):  
Vesco Mutskov ◽  
Delphine Gerber ◽  
Dimitri Angelov ◽  
Juan Ausio ◽  
Jerry Workman ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Transcription Factors ◽  
Molecular Biology ◽  
Binding Sites ◽  
Cross Linking ◽  
Uv Laser ◽  
Histone Tail ◽  
Histone Tails ◽  
Nucleosomal Dna ◽  
Core Histones

ABSTRACT In this study, we examined the effect of acetylation of the NH2 tails of core histones on their binding to nucleosomal DNA in the absence or presence of bound transcription factors. To do this, we used a novel UV laser-induced protein-DNA cross-linking technique, combined with immunochemical and molecular biology approaches. Nucleosomes containing one or five GAL4 binding sites were reconstituted with hypoacetylated or hyperacetylated core histones. Within these reconstituted particles, UV laser-induced histone-DNA cross-linking was found to occur only via the nonstructured histone tails and thus presented a unique tool for studying histone tail interactions with nucleosomal DNA. Importantly, these studies demonstrated that the NH2 tails were not released from nucleosomal DNA upon histone acetylation, although some weakening of their interactions was observed at elevated ionic strengths. Moreover, the binding of up to five GAL4-AH dimers to nucleosomes occupying the central 90 bp occurred without displacement of the histone NH2 tails from DNA. GAL4-AH binding perturbed the interaction of each histone tail with nucleosomal DNA to different degrees. However, in all cases, greater than 50% of the interactions between the histone tails and DNA was retained upon GAL4-AH binding, even if the tails were highly acetylated. These data illustrate an interaction of acetylated or nonacetylated histone tails with DNA that persists in the presence of simultaneously bound transcription factors.

scholarly journals Specific Binding of Rubidium in Chlorella

1962 ◽  
Vol 45 (5) ◽  
pp. 959-977 ◽  
Author(s):  
Dan Cohen
Keyword(s):  
Active Transport ◽  
Binding Sites ◽  
Specific Binding ◽  
High Concentration ◽  
External Concentration ◽  
Specific Binding Sites ◽  
Dense Suspension ◽  
Concentration Of Ions ◽  
The Individual ◽  
A Site

Specific binding sites for potassium, which may be components of the carriers for active transport for K in Chlorella, were characterized by their capacity to bind rubidium. A dense suspension was allowed to take up Rb86 from a low concentration of Rb86 and a high concentration of ions which saturate non-specific sites. The amount bound was derived from the increase in the external concentration of Rb86 following addition of excess potassium. The sites were heterogeneous. The average affinity of Rb and various other ions for the sites was determined by plotting the degree of displacement of Rb86 against log molar concentration of the individual ions. Interpolation gave the concentration for 50 per cent displacement of Rb, which is inversely related to affinity. The order of affinity was not changed when the cells were frozen, or boiled either in water or in 70 per cent ethanol. The affinity is maximal for ions with a crystalline radius of 1.3 to 1.5 A and a high polarizability, and is not related to the hydrated radius or valency. It is suggested that binding groups in a site are rigidly arranged, the irregular space between them being 2.6 to 3.0 A across, so that affinity is high for ions of this diameter and high polarizability.

Sign in / Sign up

Export Citation Format

Share Document