Eleven-nineteen leukemia protein YEATS domain (ENL YEATS domain)

The Eleven-nineteen leukemia protein YEATS domain is a specialized protein module found in key transcriptional co-regulators (ENL, AF9, GAS41, YEATS2). It possesses an immunoglobulin-like β-sandwich fold with a ligand-binding pocket that selectively recognizes acylated lysines (e.g., acetylation, crotonylation) on histone tails, thereby acting as an epigenetic reader[1][5]. This recognition is crucial for recruiting chromatin-modifying complexes involved in gene activation or repression. YEATS domain-containing proteins regulate transcriptional elongation, chromatin remodeling, and are implicated in cancer pathogenesis, particularly leukemia, due to their fusion with MLL in oncogenic translocations[2][4][5]. Drug discovery efforts have begun to target this domain, exploiting its role in transcriptional control and tumorigenesis[4][5].

Other names

ENL YEATS domainMLLT1YEATS1YEATS domain-containing proteinYD proteins

Inhibition of YEATS domain prevents recognition of acetylated and acylated lysine on histones, disrupting recruitment of transcriptional complexes and chromatin remodeling machinery, and potentially blocking oncogenic transcriptional programs