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

Transcriptional regulation is commonly associated with local levels of histone acetylation, which controls chromatin structure at specific genes or within contiguous chromosomal domains. Less well understood are the higher order determinants of histone acetylation. The transcription factor, CCAAT/enhancer-binding protein alpha (C/EBPalpha), concentrates at one higher order structure, the peri-centromeric chromatin, and regulates differentiation in many cell types, including pituitary cells. We used quantitative fluorescence microscopy to show that immunostained acetylated histone H3 is relatively absent from peri-centromeric domains visible as large structures in mouse pituitary progenitor GHFT1-5 cells. GHFT1-5 cells do not contain C/EBPalpha. We observed that expression of C/EBPalpha in GHFT1-5 cells leads to an increased level of acetylated histone H3, but not acetylated histone H4, at the peri-centromeric domains. Only transcriptionally active forms of C/EBPalpha altered histone acetylation at the peri-centromeric domain. The altered state of histone acetylation at large intranuclear domains may complement, counteract, or supersede the more gene-local activities of other transcription factors to coordinate C/EBPalpha-induced cellular differentiation.