Sgf29, a component of the SAGA transcriptional coactivator complex, is involved in crucial biological processes. It binds to histone H3K4me2/3, facilitating SAGA complex recruitment and histone H3 acetylation, which is important for gene regulation [4]. It also participates in histone post-translational modification as part of the Ada2/Ada3/Gcn5/Sgf29 histone acetyltransferase module [2].

In cellular senescence of human mesenchymal progenitor cells and fibroblasts, Sgf29 forms liquid-like nuclear condensates. The Arg 207 in its intrinsically disordered region is key for phase separation. These condensates, along with H3K4me3 binding, are essential for its chromatin location, recruitment of transcriptional factors, and activation of senescence-associated genes like CDKN1A [1]. In acute myeloid leukemia (AML), Sgf29 deletion impaired leukemogenesis in multiple subtype models, revealing its role in the transcription of AML oncogenes [3]. A CRISPR-based study identified Sgf29 as crucial for H3K9 acetylation, ribosomal gene expression, and leukemogenesis, and developed a drug discovery strategy targeting its Tudor domain [5].

In summary, Sgf29 is vital for gene regulation through histone modification and phase-separation-related transcriptional regulation. Its study in AML and cellular aging models has provided insights into disease mechanisms. Understanding Sgf29's functions may offer potential therapeutic targets for leukemia and aging-related research.