Chaf1bEdit

CHAF1B, short for Chromatin Assembly Factor 1 subunit B, is a core component of a highly conserved chromatin-management machine that operates at the intersection of DNA replication, DNA repair, and epigenetic maintenance. In humans, CHAF1B forms part of the CAF-1 complex, which also includes CHAF1A (the p150 subunit) and RBBP4 (the p48 subunit). This trimeric complex functions as a histone chaperone that escorts histones H3 and H4 to nascent DNA, promoting the orderly reassembly of nucleosomes as genetic material is copied and repaired. The activity of CHAF1B and CAF-1 is tightly coordinated with the replication machinery, notably through interactions with PCNA, the sliding clamp that anchors replication and repair activities at the DNA fork. CAF-1 PCNA DNA replication

CHAF1B is predominantly a nuclear protein, and its presence is essential for maintaining genome integrity in proliferating cells. Its role extends beyond simply handing histones to DNA; it is involved in preserving chromatin states after replication, contributing to the repression or activation of gene expression through chromatin organization. In this capacity, CHAF1B interfaces with broader epigenetic systems that regulate higher-order chromatin structure, histone modifications, and the propagation of chromatin states through cell divisions. Chromatin Epigenetics Histone

Structure, interactions, and mechanism - The CAF-1 complex is a heterotrimer composed of CHAF1A, CHAF1B, and RBBP4. CHAF1B provides a critical scaffold and functional surface for histone delivery during replication-coupled nucleosome assembly. CHAF1B CAF-1 - The complex is recruited to sites of DNA replication and repair via interactions with PCNA, enabling coordinated histone deposition as DNA polymerases synthesize new strands. This coupling helps preserve histone marks and chromatin structure across cell divisions. PCNA DNA replication - Histone deposition by CAF-1 predominantly involves histones H3 and H4, with CHAF1B contributing to the specificity and timing of this histone handoff during S phase and in certain DNA repair pathways. Histone Nucleosome

Cellular roles - Replication-coupled chromatin assembly: CHAF1B, through CAF-1, ensures that newly replicated DNA is promptly packaged into nucleosomes, preventing aberrant exposure of DNA and helping to maintain appropriate chromatin compaction. DNA replication Nucleosome - DNA repair and genome stability: In response to DNA damage, CAF-1–mediated histone deposition supports the restoration of chromatin structure and can influence repair pathway choice and efficiency. This function contributes to the prevention of genomic instability, a hallmark of many diseases. DNA repair Genome stability - Epigenetic maintenance: By delivering histones with their associated post-translational marks, CHAF1B helps propagate chromatin states through cell divisions, supporting stable patterns of gene expression and silencing. Epigenetics Chromatin - Interplay with other histone chaperones and replication factors: CHAF1B operates in a network with other histone chaperones (such as ASF1) and replication factors to coordinate chromatin assembly with DNA synthesis. ASF1 DNA replication

Development and regulation - Essentiality in development: CHAF1B is required for normal cell proliferation and organismal development in model systems. Disruption of CAF-1 components can lead to impaired development or embryonic lethality in certain organisms, underscoring the vital role of chromatin assembly in developmental programs. Developmental biology CHAF1B - Cell cycle control: The activity of CHAF1B-Containing CAF-1 is tightly coupled to the cell cycle, with peak involvement during S phase when DNA replication occurs. Regulation of CAF-1 activity ensures that chromatin is properly reassembled as DNA is duplicated. Cell cycle

Clinical relevance and research debates - Cancer biology: CHAF1B expression and CAF-1 activity have been investigated in cancer biology. In some contexts, elevated CHAF1B levels correlate with increased proliferation and poor prognosis, suggesting that CHAF1B can support tumor cell growth by sustaining chromatin dynamics that favor rapid division. In other contexts, CAF-1–mediated chromatin maintenance may act to preserve genome integrity and suppress mutagenesis, indicating a context-dependent role. The literature thus presents a nuanced view: CHAF1B can be seen as a facilitator of cell proliferation in some cancers and as a guardian of genome stability in others, depending on tissue type and mutational landscape. Cancer Genome stability BRCA1 - Hematopoiesis and immune cells: Given CAF-1’s role in dividing cells, CHAF1B has been studied in hematopoietic and immune lineages. Proper chromatin assembly is important for lineage specification and function, though the specifics can vary by cell type and developmental stage. Hematopoiesis Immune system - Research approaches and controversies: Studies of CHAF1B often employ knockdown or knockout models, chromatin analysis, and proteomics to map interactions. As with many chromatin regulators, interpretations can be context-dependent, with different cell types and environmental conditions highlighting distinct aspects of CHAF1B function. RNA interference Proteomics

Historical notes - Discovery and nomenclature: CHAF1B was identified as part of the CAF-1 complex, a conserved chromatin assembly factor first described in yeast and later characterized in higher eukaryotes. The naming reflects its role as the B subunit of the three-component complex that orchestrates histone deposition. Histone chaperones CAF-1

See also - CAF-1 - DNA replication - Chromatin - Histone - PCNA - Epigenetics - BRCA1 - Genome stability - Hematopoiesis - Cancer - Nucleosome