DNA replication timing regulates gene expression level. (A) Illustration of replication timing profiles from a portion of the genome of yeast (left) versus mammalian cells (right). The profiles look qualitatively similar, but the scales and the organization in terms of replication origins and activity are different (see text). (B) The work of Müller and Nieduszynski in yeast reveals that loci of conserved early replication timing, such as histone genes (exemplified by HTB1 and HTA1), require an early doubling time to achieve its maximal expression levels. They do so by escaping (green arrow shapes) the dosage compensation mechanisms occurring immediately after replication (orange shadow) that ensure expression homeostasis during S phase (orange arrow shapes). Whether a similar mechanism for regulating gene expression in a replication-dependent manner occurs in mammalian cells is currently unknown (question mark).