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#epigenetic readers

2 public questions tagged with this topic.

Chromodomains mainly bind to which modified residue?

Methyllysine-binding modules convey repressive or active marks depending context. Chromodomain, from Greek chromatin organization modifier, first found in Drosophila Polycomb and HP1 proteins, folds into three beta sheets plus alpha helix creating aromatic cage capturing trimethylated lysine side chains, especially H3K9me3 and H3K27me3 driving heterochromatin spreading silencing. Some chromodomains also bind H3K4me3 in active transcription via distinct mechanism. Unlike bromodomains recognizing acetylation, chromodomains discriminate mono di tri methyl states. Phosphothreonine recognized by FHA or BRCT domains, unmodified tails lack high affinity reader interactions, ensuring modification-specific recruitment necessary for epigenetic memory.

Ref: Bannister et al., 2001 Nature; Alberts et al., Molecular Biology of the Cell, Chapter 4: Chromodomains Bind Methylated Lysine

Bromodomains specifically recognize which histone modification?

Effector proteins interpreting histone code contain specific reader modules. Bromodomain, originally identified in Drosophila Brahma chromatin remodeling complex, forms four-helix bundle with deep hydrophobic pocket specifically accommodating acetyl-lysine side chain, preferentially H3K14ac, H3K27ac, H4K16ac. Binding recruits transcription initiation factor TFIID, SWI/SNF remodeler and p300 acetyltransferase to acetylated active chromatin stimulating gene expression. Chromodomains recognize methyllysine, 14-3-3 binds phosphoserine, no specialized domain uniquely recognizes ubiquitin alone. Bromodomain inhibition by small molecule JQ1 displaces readers blocking oncogenic transcription and inflammation, highlighting therapeutic importance for active chromatin.

Ref: Dhalluin et al., Nature 1999 Bromodomain Structure; Lodish et al., Chapter 8: Bromodomains Recognize Acetylated Lysine