The Necessity of Chromatin: A View in Perspective

Abstract

Epigenomics has grown exponentially, providing a better understanding of the mechanistic aspects of new and old phenomena originally described through genetics, as well as providing unexpected insights into the way chromatin modulates the genomic information. In this overview, some of the advances are selected for discussion and comment under six topics: (1) histone modifications, (2) weak interactions, (3) interplay with external inputs, (4) the role of RNA molecules, (5) chromatin folding and architecture, and, finally, (6) a view of the essential role of chromatin transactions in regulating the access to genomic DNA.

Figure 1.

Transcriptional memory of the chromatin state. The schematic drawing illustrates some key changes in the chromatin marks associated with a chromatin region that has recently been transcribed or becomes stably repressed by Polycomb mechanisms. A region that has not been recently transcribed is marked by heavy H3K27me2. A region recently transcribed has lost H3K27me2, but instead gained H3K27ac and H3K4me3 marks in the promoter-proximal part and H3K36me3 (which, in turn, recruits deacetylating complexes) to control the excessive access allowed by the loss of H3K27me2. Regions that can recruit stable binding of Polycomb complexes PRC1 and PRC2 acquire H3K27me3. For simplicity, other histone marks are not shown.

Figure 2.

A model for the control of DNA accessibility in chromatin. (A) The model proposes that antagonistic roaming activities transiently interact with genomic chromatin: one, caused by PRC2, deposits the H3K27me2 mark. Another removes this methylation mark and remodels nucleosomes, allowing transient access to the DNA sequence. These activities are attributed to UTX, CBP, and BRAHMA. (B) A DNA-binding factor A binds to its cognate binding motif in the DNA, transiently made accessible, and recruits stable binding of CBP together with a remodeling activity (BRAHMA) and the TRR/MLL3,4 complex containing UTX. These activities remove H3K27 methylation, depositing instead the H3K27ac and H3K4me1 marks. (C) The remodeling activity provides stable access to the DNA, leading to the binding of additional factors B and C to an enhancer region (or other regulatory element on the DNA). The region of DNA made accessible can also be opportunistically targeted by RNA polymerase, which may produce short transcripts from both DNA strands.