Pioneering the developmental frontier

Larson, Elizabeth D; Marsh, Audrey J.; Harrison, Melissa M.

doi:10.1016/j.molcel.2021.02.020

Cited by 56 publications

(49 citation statements)

References 88 publications

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“…The pioneer factor model postulates that the majority of TFs display low affinity for nucleosomal DNA while only a specialized subset of TFs, termed pioneer factors, have the ability to engage chromatinized binding sites both in vitro and in cells (Cirillo et al, 1998;Zaret, 2020). Pioneer factor engagement of chromatinized target sites has been frequently linked to subsequent binding of other TFs, cofactors, or chromatin remodelers to cause lower nucleosomal occupancy and regulate gene expression (Larson et al, 2021;Zaret, 2020). To be classified as a pioneer factor further entails the ability to initiate cell fate changes or to reprogram gene regulatory networks, in particular when sequence motifs are located in transcriptionally inactive, closed chromatin (Zaret, 2020).…”

Section: Recognition Of Site-specific Dna Motifs In the Context Of A Nucleosomementioning

confidence: 99%

Reading the chromatinized genome

Michael

Thomä

2021

Cell

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Section: Recognition Of Site-specific Dna Motifs In the Context Of A Nucleosomementioning

confidence: 99%

Reading the chromatinized genome

Michael

Thomä

2021

Cell

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“…However, the ability of enhancers to recruit their cognate TFs may be constrained by inaccessible (“closed”) chromatin conformation, whereby enhancer regions are tightly packaged in nucleosomes. A subset of TFs known as pioneer factors are capable of overcoming this constraint through chromatin remodelling (reviewed in [ 31 , 32 ]). Pioneer factors play particularly important roles in priming enhancers in order to program gene expression patterns during early development.…”

Section: Organisation and Function Of Enhancers In Cismentioning

confidence: 99%

Transcriptional enhancers and their communication with gene promoters

Ray-Jones

Spivakov

2021

Cell. Mol. Life Sci.

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Transcriptional enhancers play a key role in the initiation and maintenance of gene expression programmes, particularly in metazoa. How these elements control their target genes in the right place and time is one of the most pertinent questions in functional genomics, with wide implications for most areas of biology. Here, we synthesise classic and recent evidence on the regulatory logic of enhancers, including the principles of enhancer organisation, factors that facilitate and delimit enhancer–promoter communication, and the joint effects of multiple enhancers. We show how modern approaches building on classic insights have begun to unravel the complexity of enhancer–promoter relationships, paving the way towards a quantitative understanding of gene control.

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“…In order for DNA binding TFs to access enhancers, histone proteins undergo covalent modifications at specific sites that relax their otherwise tight association with genomic DNA, which then assumes an "open chromatin" conformation (Figure 2C; Boland et al, 2014). These histone modifications are regulated by specific classes of enzymes, and in some cases, by a group of TFs known as "pioneer factors" that can bind to their sites in nucleosomal DNA in a "closed configuration" and recruit factors that result in opening of chromatin and binding of larger transcriptional complexes (Larson et al, 2021). In this manner, enhancers can "read out" the nuclear regulatory environment to determine whether a specific gene should be transcribed.…”

Section: Organization Of Genomic Dna In the Nucleus Facilitates Transcriptionmentioning

confidence: 99%

Transcriptional and Epigenetic Landscape of Cardiac Pacemaker Cells: Insights Into Cellular Specialization in the Sinoatrial Node

2021

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Cardiac pacemaker cells differentiate and functionally specialize early in embryonic development through activation of critical gene regulatory networks. In general, cellular specification and differentiation require that combinations of cell type-specific transcriptional regulators activate expression of key effector genes by binding to DNA regulatory elements including enhancers and promoters. However, because genomic DNA is tightly packaged by histones that must be covalently modified in order to render DNA regulatory elements and promoters accessible for transcription, the process of development and differentiation is intimately connected to the epigenetic regulation of chromatin accessibility. Although the difficulty of obtaining sufficient quantities of pure populations of pacemaker cells has limited progress in this field, the advent of low-input genomic technologies has the potential to catalyze a rapid growth of knowledge in this important area. The goal of this review is to outline the key transcriptional networks that control pacemaker cell development, with particular attention to our emerging understanding of how chromatin accessibility is modified and regulated during pacemaker cell differentiation. In addition, we will discuss the relevance of these findings to adult sinus node function, sinus node diseases, and origins of genetic variation in heart rhythm. Lastly, we will outline the current challenges facing this field and promising directions for future investigation.

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Pioneering the developmental frontier

Cited by 56 publications

References 88 publications

Reading the chromatinized genome

Reading the chromatinized genome

Transcriptional enhancers and their communication with gene promoters

Transcriptional and Epigenetic Landscape of Cardiac Pacemaker Cells: Insights Into Cellular Specialization in the Sinoatrial Node

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