CCAAT/enhancer-binding protein alpha alters histone H3 acetylation at large subnuclear domains

Transcriptional regulation is commonly associated with local levels of hist one acetylation, which controls chromatin structure at specific genes or wi thin contiguous chromosomal domains. Less well understood are the higher or der determinants of histone acetylation. The transcription factor, CCAAT/en hancer-binding protein alpha (C/EBP alpha), concentrates at one higher orde r structure, the peri-centromeric chromatin, and regulates differentiation in many cell types, including pituitary cells. We used quantitative fluores cence microscopy to show that immunostained acetylated histone H3 is relati vely absent from peri-centromeric domains visible as large structures in mo use pituitary progenitor GHFT1-5 cells. GHFT1-5 cells do not contain C/EBP alpha. We observed that expression of C/EBP alpha in GHFT1-5 cells leads to an increased level of acetylated historic H3, but not acetylated historic H4, at the peri-centromeric domains. Only transcriptionally active forms of C/EBP alpha altered histone acetylation at the peri-centromeric domain. Th e altered state of histone acetylation at large intranuclear domains may co mplement, counteract, or supercede the more gene-local activities of other transcription factors to coordinate C/EBP alpha -induced cellular different iation.