Transcription factors: from enhancer binding to developmental control

  title={Transcription factors: from enhancer binding to developmental control},
  author={François Spitz and Eileen E. M. Furlong},
  journal={Nature Reviews Genetics},
Developmental progression is driven by specific spatiotemporal domains of gene expression, which give rise to stereotypically patterned embryos even in the presence of environmental and genetic variation. Views of how transcription factors regulate gene expression are changing owing to recent genome-wide studies of transcription factor binding and RNA expression. Such studies reveal patterns that, at first glance, seem to contrast with the robustness of the developmental processes they encode… 

Enhancer function: mechanistic and genome-wide insights come together.

Transcriptional enhancers and their communication with gene promoters

Classic and recent evidence on the regulatory logic of enhancers is synthesised, including the principles of enhancer organisation, factors that facilitate and delimit enhancer–promoter communication, and the joint effects of multiple enhancers.

Using synthetic biology to study gene regulatory evolution.

Enhancer and super‐enhancer: Positive regulators in gene transcription

The history, importance, advances and challenges on enhancer and super‐enhancer field are reviewed to benefit the understanding of their function mechanism for transcription underlying precise gene expression.

Developmental dynamics of transcription and genome architecture

The work described in this thesis aims to study the genome conformation/interactome and their effect on gene regulation and to unveil the role of transcription factor proteins (TFs) in complex developmental processes.

Gene activation by metazoan enhancers: Diverse mechanisms stimulate distinct steps of transcription

New high‐throughput experimental frameworks offer the opportunity to integrate and generalize disparate mechanisms identified at single genes, especially important if the authors are to fully understand how sequence variation within enhancers contributes to human disease.



Enhancer function: new insights into the regulation of tissue-specific gene expression

Surprisingly, cohesin and non-coding RNAs are emerging as crucial players responsible for facilitating enhancer–promoter interactions at some genes and may be required not only to facilitate initiation of transcription but also to activate the release of RNA polymerase II from promoter-proximal pausing.

Information display by transcriptional enhancers

It is shown that a simple, compact enhancer is capable of representing both repressed and activated states at the same time and in the same nucleus, suggesting that closely apposed factor binding sites, situated within compact cis-elements, can be independently interpreted by the transcriptional machinery.

Combinatorial binding predicts spatio-temporal cis-regulatory activity

A novel approach to predict spatio-temporal cis-regulatory activity based only on in vivo transcription factor binding and enhancer activity data is used, generating a high-resolution atlas of cis-Regulatory modules describing their temporal and combinatorial occupancy during Drosophila mesoderm development.

A core transcriptional network for early mesoderm development in Drosophila melanogaster.

It is suggested that Twist binds to almost all mesodermal CRMs to provide the competence to integrate inputs from more specialized transcription factors, and extensive combinatorial binding, feed-forward regulation, and complex logical outputs as prevalent features are revealed.

Histone H3K27ac separates active from poised enhancers and predicts developmental state

The epigenetic landscape of enhancer elements in embryonic stem cells and several adult tissues in the mouse is interrogated and it is found that histone H3K27ac distinguishes active enhancers from inactive/poised enhancers and poised enhancer networks provide clues to unrealized developmental programs.