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Interactions of Transcription Factors with Chromatin

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A Handbook of Transcription Factors

Part of the book series: Subcellular Biochemistry ((SCBI,volume 52))

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Abstract

Sequence-specific transcription factors (TFs) play a central role in regulating transcription initiation by directing the recruitment and activity of the general transcription machinery and accessory factors. It is now well established that many of the effects exerted by TFs in eukaryotes are mediated through interactions with a host of coregulators that modify the chromatin state, resulting in a more open (in case of activation) or closed conformation (in case of repression). The relationship between TFs and chromatin is a two-way street, however, as chromatin can in turn influence the recognition and binding of target sequences by TFs. The aim of this chapter is to highlight how this dynamic interplay between TF-directed remodelling of chromatin and chromatin-adjusted targeting of TF binding determines where and how transcription is initiated, and to what degree it is productive.

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  1. Banting and Best Department of Medical Research, University of Toronto, Toronto, ON, Canada, M5S 3E1

    Harm van Bakel

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    Timothy R. Hughes

Glossary

Chromatin

The combination of DNA and accessory proteins, such as histones, that together constitute chromosomes.

Transcriptional coregulator

An accessory factor recruited by transcription factors to modulate gene expression. Cofactors typically lack intrinsic DNA binding specificity and rely on transcription factors for targeting. Most cofactors excert their effects by locally modifying chromatin structure.

Transcriptional coactivator

A coregulator that positively affects gene expression.

Transcriptional corepressor

A coregulator that negatively affects gene expression.

Chromatin modifiers

Proteins or protein complexes that can effect changes in chromatin structure by covalently modifying histones or moving nucleosomes. In this chapter the term chromatin modifier is used generally to refer to histone modifiers and ATPase nucleosome remodelers.

Histone modifiers

The enzymes responsible for adding or removing covalent modifications on histones, the majority of which are are found on the flexible histone tails. Some histone modifiers, such as HDACs and HATs can also have non-histone targets.

ATPase nucleosome remodelers

Protein complexes that use the energy generated by ATP hydrolysis to alter nucleosome-DNA interactions and displace nucleosomes.

Heterochromatin

A tightly packed form of chromatin where DNA is typically rendered inaccessible to the transcriptional machinery. Different types of heterochromatin are associated with distinct chromatin marks, such as HP1 heterochromatin (HP1 binding and H3K9me) or Polycomb domains (H3K27me).

Euchromatin

An open chromatin conformation in which DNA is easily accessible. This type of chromatin is often, but not exclusively, associated with active transcription.

Histone code

Distinct patterns of histone modifications are believed to constitute a code that is used to direct specific activities on DNA, such as during transcriptional silencing or during the various stages of the transcriptional cycle. For example, the initiation, elongation and termination of transcription are each associated with different patterns of histone modifications that are believed to contribute to the recruitment and regulation of the proteins required in each stage.

Epigenetics

Inherited changes in phenotypes or expression profiles that are not due to changes in the underlying DNA sequence. Examples of epigenetic modifications include DNA methylation and covalent histone modifications, which play an important role in a variety of processes, including cell differentiation, X chromosome inactivation and imprinting.

Polycomb-group proteins

A family of proteins, initially discovered in Drosophila, that are involved in epigenetic silencing of genes by inducing a repressive chromatin structure. Polycomb group proteins are predominantly found as part of two main protein complexes: Polycomb-group Repressive Complex 1 and 2 (PRC1 and PRC2).

Nucleosome

The basic building block of chromatin, consisting of ~147 bp of DNA wrapped around an octamer of two of each of the histones H2A, H2B, H3 and H4.

Effector domains

The domains in transcription factors that are responsible for mediating their effects on gene expression. These effects can be activating or inhibitory and involve a variety of mechanisms, including recruitment of chromatin modifiers, or interactions with components of the basal transcriptional machinery and other transcription factors.

DNA binding domain

A protein domain with DNA binding activity. In the case of transcription factors, these domains typically possess specificity affinity for a limited number of DNA sequences.

Enhancer

A DNA element bound by transcription factors that can operate over long distances (up to thousands of basepairs) to stimulate transcription of its target gene(s). Enhancers are thought to operate through looping interactions with promoter regions. In addition to their distance to genes, enhancers can also be distinguished from promoters by a unique chromatin profile. Though most enhancers act in cis, they can also be located on different chromosomes.

Silencer

Like enhancers, silencers are DNA elements that can be located far away from the genes they control, but their effect on gene expression is negative. Silencers can also act as nucleation sites for repressive chromatin domains.

Insulator

A DNA element that either prevents an enhancer from activating target genes, or acts as a boundary element to delineate different chromatin domains. Insulators are distinct from from silencer regions in that an insulator needs to be located between an enhancer and a gene to affect expression, while silencers can typically operate in any orientation relative to a gene.

Chromatin domain

A relatively uniform region of chromatin characterized by distinct histone and/or DNA modifications. Examples include Polycomb domains as well as telomeric- and pericentromeric heterochromatin.

Preinitiation complex

Large complex of proteins required for successful transcription initiation by RNA Polymerase II. Major components include the basal transcription factors TFIIA, TFIIB, TFIID, TFIIE, TFIIF, and TFIIH. The preinitiation complex plays a role in positioning polymerase and melting the DNA so that it is properly configured to fit in the active site. Positioning is aided by motifs recognized by the general transcription factors.

CpG island

Sequence elements rich in CG dinucleotides that are found at a large number of mammalian promoters.

General transcription factors

Transcription factors that are universally required for RNA polymerase II transcription. Most GTFs are part of the preinitiation complex.

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van Bakel, H. (2011). Interactions of Transcription Factors with Chromatin. In: Hughes, T. (eds) A Handbook of Transcription Factors. Subcellular Biochemistry, vol 52. Springer, Dordrecht. https://doi.org/10.1007/978-90-481-9069-0_11

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