Epigenetic reader domains can be thought of as effector proteins that recognize and are recruited to specific marks on histones or nucleotides. Enzymes which "write" or "erase" epigenetic marks may also contain such reader domains, leading to the coordination of "read-write" or "read-erase" epigenetic processes.
The structure of reader domains typically provides a cavity or surface groove in which to accommodate a specific epigenetic mark. Interactions between the reader domain and the flanking sequence of the modified amino acid also allows the reader domain-containing protein to distinguish between similar epigenetic marks, for example between histone lysine mono-, di- and trimethylation.
Proteins that contain reader domains can be broadly classified into four groups: chromatin architectural proteins, chromatin remodeling enzymes, chromatin modifiers, and adaptor proteins that recruit other machinery involved in gene expression. The first group of these, chromatin architectural proteins, bind to nucleosomes and can either directly induce chromatin compaction or alternatively act as a shield to prevent the binding of proteins involved in RNA transcription. Through self-propagation and oligomerization, these chromatin architectural proteins can exert their inhibitory effect on transcription over a significant length of DNA.
In contrast to chromatin architectural proteins, chromatin remodeling enzymes prompt a more open chromatin architecture; the increased accessibility of chromatin facilitates DNA transcription. This structural shift in chromatin architecture is driven by the energy of ATP hydrolysis. One such example is the yeast chromatin remodeling enzyme complex, RSC, which contains a tandem bromodomain within its Rsc4 subunit that recruits the complex to acetylated lysine residues on histone H3 (H3K14). RSC is involved in a number of cellular processes including nucleosome remodeling, the consequence of which is the promotion of RNA polymerase II recruitment to the underlying DNA, prompting gene transcription.
Aside from chromatin remodeling enzymes and architectural proteins, many other proteins that contain reader domains cannot directly influence chromatin architecture, but instead serve to recruit secondary chromatin modifiers to further modify chromatin or to reverse an existing chromatin modification. The corepressor complex Sin3S is recruited to methylated histone lysine residues through a Sin3 tandem bromodomain. Since histone deacetylases HDAC1, HDAC2 and HDAC3 are also found within the Sin3S complex, the recruitment of this complex prompts a secondary histone modification: histone deacetylation.
The final class of reader domain-containing proteins is adaptor proteins: the principal function of these domains is to recruit factors that are linked to DNA metabolism processes including transcription, DNA damage repair, DNA recombination, DNA replication and RNA processing. Interaction of the BRCT domain of MDC1 - a critical mediator of the DNA damage response - with a phosphorylated serine residue on histone H2AX acts as an adaptor to recruit the histone ubiquitin ligase, RNF8, to double-strand break-flanking chromatin. Subsequent histone ubiquitination itself recruits repair machinery including tumor protein p53 binding protein 1 (TP53BP1).Back to Epigenetics »