Transcriptional interference among the murine beta-like globin genes

Mammalian beta-globin loci contain multiple genes that are activated at different developmental stages. Studies have suggested that the transcription of one gene in a locus can influence the expression of the other locus genes. The prevalent model to explain this transcriptional interference is that all potentially active genes compete for locus control region (LCR) activity. To investigate the influence of transcription by the murine embryonic genes on transcription of the other beta-like genes, we generated mice with deletions of the promoter regions of Ey and beta h1 and measured transcription of the remaining genes. Deletion of the Ey and beta h1 promoters increased transcription of beta major and beta minor 2-fold to 3-fold during primitive erythropoiesis. Deletion of Ey did not affect beta h1 nor did deletion of beta h1 affect Ey, but Ey deletion uniquely activated transcription from beta h0, a beta-like globin gene immediately downstream of Ey. Protein analysis showed that beta h0 encodes a translatable beta-like globin protein that can pair with alpha globin. The lack of transcriptional interference between Ey and beta h1 and the gene-specific repression of beta h0 did not support LCR competition among the embryonic genes and suggested that direct transcriptional interference from Ey suppressed beta h0.