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The two divergently transcribed H2A-H2B gene pairs in yeast are differentially regulated as a function of the copy number of histone genes. Transcription of an HTA2-lacZ reporter gene is independent of histone gene copy number. Transcription of an HTA1-lacZ gene can be repressed or derepressed, depending on the number of HTA plus HTB genes in cells. Regulation by histone gene dosage is dependent on a negative site in the HTA1-HTB1 promoter and the products of regulatory genes that act through this site. The level of H2A plus H2B protein in the cell may signal the response to histone gene copy number, suggesting that transcription of the HTA1-HTB1 locus can be autogenously regulated. This phenomenon may be used, in part, to maintain the balanced synthesis of histones, a critical parameter in nucleosome assembly.

A yeast H2A-H2B promoter can be regulated by changes in histone gene copy number.