Linker histone transitions during mammalian oogenesis and embryogenesis.

A unique characteristic of the oocyte is that, although it is a differentiated cell, it can to give rise to a population of undifferentiated embryonic cells. This transition from a differentiated to a totipotential condition is thought to be mediated in part by changes in chromatin composition or configuration. In many non-mammalian organisms, oocytes contain unique subtypes of the linker histone H1, which are replaced in early embryos by the so-called somatic histone H1 subtypes. We review evidence that such histone H1 subtype switches also occur in mammals. Immunologically detectable somatic H1 is present in mitotically proliferating oogonia but gradually becomes undetectable after the oocytes enter meiosis. Immunoreactive somatic H1 remains undetectable throughout oogenesis and the early cell cycles after fertilization. Following activation of the embryonic genome, it is assembled onto chromatin. In contrast to the absence of immunoreactive protein, mRNAs encoding each of the five mammalian somatic H1 subtypes are present in growing oocytes and newly fertilized embryos, indicating that post-transcriptional mechanisms regulate expression of these genes. This maternal mRNA is degraded at the late 2-cell stage, and embryonically encoded mRNAs accumulate after embryos reach the 4-cell stage. During the period when somatic H1 is not detectable, oocytes and embryos contain mRNA encoding a sixth subtype, histone H1(0) which accumulates in differentiated somatic cells, and the nuclei can be stained with an H1(0)-specific antibody. We propose that the linker histone composition of the oocyte lineage resembles that of other mammalian cells, namely, that the somatic H1 subtypes predominate in mitotically active oogonia, that histone H1(0) becomes prominent in differentiated oocytes, and that following fertilization and transcriptional activation of the embryonic somatic H1 genes, the somatic H1 subtypes are reassembled onto chromatin of the embryonic cells. Potential functions of these linker histone subtype switches are discussed, including stabilization by H1(0) of the differentiated state of the oocytes, protection of the oocyte chromatin from factors that remodel sperm chromatin after fertilization, and restoration by the incorporation of the somatic H1 subtypes of the totipotential state of embryonic nuclei.