Chromatin organization and modifications regulating transcription

Daniela Ramos-Cruz

In eukaryotes, DNA is tightly packed and functionally organized inside the nucleus. From a megabase to a local scale, the hierarchical chromatin organization influences several fundamental cellular processes, including transcription, replication, and DNA repair. At the base of this hierarchical organization is the nucleosome, which consists of 147 bp of DNA wrapped around an octamer of histone proteins. Chromatin accessibility at the nucleosomal level is regulated by the combined action of two classes of proteins: histone-modifying enzymes and chromatin remodelers. Together, they coordinate the cellular processes dictated by the genome in response to developmental or environmental stimuli.

Histone-modifying enzymes post-translationally modify the N-terminal tails of histone proteins through acetylation, phosphorylation, ubiquitination, ADP-ribosylation, or methylation. These histone modifications can be reversed by a set of antagonistic enzymes catalyzing the removal of chemical modifications. The combinatorial arrangement of histone marks defines and partitions the genome into functional domains, such as transcriptionally silent heterochromatin and transcriptionally active euchromatin. For instance, histone acetylation has generally been associated with transcriptional activation, whereas histone ubiquitination most frequently plays a role in transcriptional repression and histone methylation has been involved in both, transcriptional activation and silencing. The local combination of inter-related histone modifications forms the “histone code”, which is interpreted by effector proteins or “readers” that recognize and bind to modifications through specific domains to regulate transcription.

The second class of chromatin-modifying factors are the ATP-dependent chromatin-remodeling enzymes. ATP-dependent chromatin remodelers alter nucleosomal structure and DNA accessibility. They mediate gene activation by repositioning (slide, twist, or loop) of nucleosomes along the DNA, evicting histones, or facilitating exchange of histone variants. ATP chromatin remodelers are categorized according to their biochemical activities and ATPase subunit similarity into four different subfamilies: Switching Defective/Sucrose Non-Fermenting (SWI/SNF), Imitation Switch (ISWI), Chromatin Helicase DNA-Binding (CHD) and Inositol Requiring (INO80). ISWI and CHD families participate in nucleosome spacing in chromatin assembly after replication; SWI/SNF subfamilies are important for nucleosomal disassembly, and INO80 and SWR1 complexes have opposite roles in histone variant exchange.

In this chapter we will describe the current knowledge about chromatin organization, from higher order chromatin structures to nucleosomal local scale. We will then describe the different histone modifications and chromatin remodelers and their role in regulating chromatin modifications and transcription to control cellular and physiological responses in plants.