GO:0140118 histone H3K23ac reader activity

Histone acetylation is a central epigenetic mechanism that regulates chromatin accessibility and gene expression. Among the many acetylation marks on histone H3, acetylation at lysine 23 (H3K23ac) has emerged as a distinct non-canonical signature recognized by dedicated reader proteins. GO:0140118, histone H3K23ac reader activity, defines the molecular function of proteins that bind histone H3 specifically when it is acetylated at lysine 23. This activity is essential for translating the H3K23ac mark into downstream biological outcomes, including lineage specification and immune regulation. The H3K23ac mark is deposited by the histone acetyltransferase MORF (KAT6B), which couples H3K23 acetylation to H3K14 acylation, thereby generating a composite chromatin signature that can be interpreted by reader modules. The tandem PHD-bromodomain module of TRIM24 is a well-characterized H3K23ac reader, and its recognition of this non-canonical histone signature links H3K23ac to breast cancer pathogenesis. Structural and biochemical studies of TRIM24 have provided mechanistic insight into how acetylated histone tails are recognized by reader modules. For researchers, GO:0140118 provides a precise functional annotation to study how H3K23ac is decoded in development, ageing and disease. Recent work demonstrates that epigenetic programming by H3K23ac defines the lineage fate of Meg3(+) haematopoietic stem cells and drives immune ageing, underscoring the physiological importance of this reader activity. Understanding the proteins, mechanisms and regulatory contexts of H3K23ac recognition is therefore critical for both basic chromatin biology and therapeutic development.

GO:0140118 (histone H3K23ac reader activity) is a molecular_function term defined as a histone reader that recognizes histone H3 acetylated at lysine 23. In other words, it describes the selective binding activity of proteins that detect the H3K23ac mark on chromatin. The synonym histone H3K23ac modified histone binding reflects the same concept. This activity is distinct from the enzymatic writers and erasers of the mark; it is the recognition step that converts the H3K23ac modification into functional outputs such as recruitment of transcriptional co-regulators or chromatin remodeling complexes.

GO:0140118 is important because it defines the molecular function that decodes the H3K23ac mark, a non-canonical histone acetylation event with critical roles in development, stem cell biology and disease. The H3K23ac mark is deposited by MORF (KAT6B) in a coupled reaction with H3K14 acylation, creating a composite signature that requires dedicated readers for interpretation. Reader proteins such as TRIM24 recognize this signature and link it to oncogenic transcriptional programs in breast cancer. More recently, H3K23ac reader activity has been shown to define the lineage fate of Meg3(+) haematopoietic stem cells and to drive immune ageing, highlighting its physiological relevance beyond cancer. Studying this activity therefore provides mechanistic insight into how epigenetic marks are translated into cell fate decisions and disease phenotypes.

The following genes and proteins are directly implicated in H3K23ac writer, reader and regulatory functions based on published literature.

H3K23ac reader activity is regulated at multiple levels. The deposition of the mark itself is controlled by MORF (KAT6B), which couples H3K23 acetylation to H3K14 acylation, thereby creating a composite signature that influences reader binding. The abundance and accessibility of H3K23ac readers such as TRIM24 are regulated in a context-dependent manner, with implications for breast cancer pathogenesis. Additionally, cross-talk with other histone modification systems, such as the MRG1/2 methylation reader complex that associates with HD2C deacetylase, can modulate the chromatin landscape and indirectly affect H3K23ac recognition. Developmental and environmental cues, including day-length changes in plants, can influence related reader complexes, suggesting that H3K23ac reader activity may also be subject to external regulation. In haematopoietic stem cells, H3K23ac-dependent epigenetic programming is linked to immune ageing, indicating that ageing-related pathways may regulate this activity.

TRIM24, a prototypical H3K23ac reader, links a non-canonical histone signature to breast cancer. The tandem PHD-bromodomain module of TRIM24 recognizes H3K23ac and mediates oncogenic transcriptional programs that promote tumorigenesis. Structural studies of the TRIM24 PHD-Bromo module have provided a mechanistic basis for how this reader engages acetylated histone tails, offering potential avenues for therapeutic intervention. Dysregulation of H3K23ac reader activity may therefore contribute to breast cancer development and progression.

Epigenetic programming by H3K23ac defines the lineage fate of Meg3(+) haematopoietic stem cells and drives immune ageing. This indicates that H3K23ac reader activity is not only relevant to cancer but also to age-related decline in immune function. The Meg3(+) haematopoietic stem cell subset is programmed by H3K23ac, and disruption of this programming contributes to immune ageing phenotypes. These findings position H3K23ac reader activity as a potential target for interventions aimed at preserving immune function during ageing.

The H3K23ac mark is deposited by MORF (KAT6B) in a coupled reaction with H3K14 acylation, and mutations in KAT6B are associated with developmental disorders. Although direct links between H3K23ac reader activity and specific developmental syndromes remain to be fully established, the role of MORF in generating this composite signature suggests that impaired reader recognition could contribute to chromatin-related pathologies. Cross-talk with other histone reader systems, such as MRG1/2 and HD2C, further highlights the potential for H3K23ac reader dysfunction in broader epigenetic disorders.

Chromatin immunoprecipitation (ChIP) using antibodies against H3K23ac or tagged reader proteins can map the genomic localization of the mark and its readers. In vitro binding assays with recombinant reader domains and modified histone peptides are used to measure direct recognition of H3K23ac. These methods are essential for validating candidate readers identified through bioinformatics or screening approaches.

RNA-seq and related transcriptomic methods measure changes in gene expression upon perturbation of H3K23ac reader activity, such as knockout or overexpression of TRIM24 or MORF. Integration with epigenomic data, including ATAC-seq and ChIP-seq, provides a comprehensive view of how H3K23ac recognition influences chromatin accessibility and transcriptional programs.

Affinity purification coupled with mass spectrometry can identify proteins that associate with H3K23ac-modified histones or with reader complexes. These approaches help define the composition of reader-containing complexes and identify cofactors that mediate downstream effects. Proteomic profiling of histone modifications can also quantify H3K23ac levels in different biological conditions.

X-ray crystallography, NMR and isothermal titration calorimetry are used to determine the structural basis of H3K23ac recognition by reader modules such as the TRIM24 PHD-bromodomain. These methods reveal the molecular determinants of specificity and affinity, guiding the design of mutations that disrupt reader function.

Researchers studying histone H3K23ac reader activity-related genes often need to determine whether a candidate gene is causally involved in mark recognition, chromatin regulation and disease phenotypes. EDITGENE provides comprehensive CRISPR-based services to generate knockout, point-mutation, knock-in and overexpression cell models, as well as CRISPR library screening and bioinformatics support, enabling rigorous functional dissection of H3K23ac reader biology.

GO:0140118 (histone H3K23ac reader activity) defines a critical molecular function that translates the non-canonical H3K23ac mark into biological outcomes. The mark is deposited by MORF (KAT6B) in a coupled reaction with H3K14 acylation, and reader proteins such as TRIM24 recognize this composite signature to regulate gene expression programs. This activity is implicated in breast cancer and in haematopoietic stem cell lineage fate and immune ageing, underscoring its broad physiological and pathological relevance. Researchers can leverage CRISPR knockout, point-mutation, knock-in and overexpression models, combined with transcriptomic, epigenomic and structural approaches, to dissect the causal roles of H3K23ac readers. EDITGENE provides end-to-end services to accelerate these studies and advance our understanding of H3K23ac reader biology in health and disease.