Background: Not much is known about epigenomic changes during the differentiation of human stem cells into mature enucleated red cells. Results: Methylome analysis during human erythropoiesis revealed that global hypomethylation occurs during this process and correlates with transcriptomic changes. Conclusion: Integrative analysis also allowed us to identify novel regulatory areas of the genome. Significance: Progressive functional hypomethylation during human erythroid differentiation changes the current paradigm.

Mammalian H1 histones consist of a group of at least seven protein subtypes including the somatic H1s, H1a to H1e, the testis-specific H1t, and the replacement linker histone H1Њ (50). These proteins bind to the linker DNA between nucleosome cores and facilitate the formation of higher-order chromatin structures (1, 67). The large number and different patterns of expression of the H1 subtypes suggest that they are in part responsible for the variations in chromatin structure that exist within the genome and during development. H1 histones have been postulated to play a role in repression of transcription (69), and recent in vitro experiments support this view (18,48).The H1Њ subtype is the smallest and most lysine-rich member of the H1 family. Its amino acid sequence is more closely related to the erythroid cell-specific linker histone H5, present in nucleated erythrocytes of birds, fish, and amphibians, than to the other H1 subtypes (23).

that interferon is able to increase the rate of Friend cell differentiation. MATERIALS AND METHODS Cell line. All experiments were made with cells grown from clone 745 of the original Friend cell line (6), kindly donated to us by C. Friend

According to the masked maternal messenger RNA hypothesis, a large part if not all the protein synthesis of early development is directed by mRNA already present in the cytoplasm of unfertilized eggs. This mRNA is supposed to be synthesized during oogenesis and stored in some unavailable form until some later time in development, when it is selectively associated with the translational machinery. To the indirect evidence, which is nevertheless very strong, there can now be added a direct proof of the hypothesis for the case of histone mRNA. The five main histones of sea urchin embryos are synthesized on small polyribosomes, directed in part by newly-synthesized messages that sediment as a group at about 9S. Some histone synthesis survives total transcription block, however, suggesting that maternal histone mRNA exists. In competition-hybridization experiments, the egg RNA is shown to contain sequences characteristic of functional, embryonic histone mRNA. The competing RNA is localized in ribonucleoprotein particles of egg homogenates that sediment at 20–40S. These same particles contain RNA that stimulates a cell-free heterologous system to synthesize sea urchin histones. The application of these facts to some problems of translation control and of development generally is discussed.

No abstract