title: The physical size of transcription factors is key to transcriptional regulation in chromatin domains.
abstract: Genetic information, which is stored in the long strand of genomic DNA as chromatin, must be scanned and read out by various transcription factors. First, gene-specific transcription factors, which are relatively small (∼50 kDa), scan the genome and bind regulatory elements. Such factors then recruit general transcription factors, Mediators, RNA polymerases, nucleosome remodellers, and histone modifiers, most of which are large protein complexes of 1-3 MDa in size. Here, we propose a new model for the functional significance of the size of transcription factors (or complexes) for gene regulation of chromatin domains. Recent findings suggest that chromatin consists of irregularly folded nucleosome fibres (10 nm fibres) and forms numerous condensed domains (e.g., topologically associating domains). Although the flexibility and dynamics of chromatin allow repositioning of genes within the condensed domains, the size exclusion effect of the domain may limit accessibility of DNA sequences by transcription factors. We used Monte Carlo computer simulations to determine the physical size limit of transcription factors that can enter condensed chromatin domains. Small gene-specific transcription factors can penetrate into the chromatin domains and search their target sequences, whereas large transcription complexes cannot enter the domain. Due to this property, once a large complex binds its target site via gene-specific factors it can act as a 'buoy' to keep the target region on the surface of the condensed domain and maintain transcriptional competency. This size-dependent specialization of target-scanning and surface-tethering functions could provide novel insight into the mechanisms of various DNA transactions, such as DNA replication and repair/recombination.
authors.affiliation: Biological Macromolecules Laboratory, Structural Biology Center, National Institute of Genetics, Mishima, Shizuoka 411-8540, Japan. Department of Genetics, School of Life Science, Graduate University for Advanced Studies (Sokendai), Mishima, Shizuoka 411-8540, Japan.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Maeshima
authors.forename: Kazunari
authors.initials: K
authors.lastname: Kaizu
authors.forename: Sachiko
authors.initials: S
authors.lastname: Tamura
authors.forename: Tadasu
authors.initials: T
authors.lastname: Nozaki
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Kokubo
authors.forename: Koichi
authors.initials: K
authors.lastname: Takahashi
mesh_terms: D002843:Chromatin / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D008958:Models, Molecular; D008970:Molecular Weight; D009010:Monte Carlo Method; D017434:Protein Structure, Tertiary; D014157:Transcription Factors / Q000737:chemistry* / Q000378:metabolism*; D014158:Transcription, Genetic; D015533:Transcriptional Activation
chemical_list: D002843:Chromatin; D014157:Transcription Factors