Developmental and hormonal regulation of protein H1 degrees in rodents.

Abstract

The tissue and cellular distribution and regulation ofthe chromatin protein HI' has been examined in developing and adult mouse and in rat. The protein appears in specific cell types of solid tissues only when the cells have terminated their maturation. This was found for brain, retina, striated and cardiac muscle, and liver. In tissues that depend on hormones for their function and maintenance, the expression of HI' is dependent on the continued presence of the specific maintenance hormone. In regenerating rat liver the amount of HI0 decreases to one-third after the onset of DNA synthesis. The possible role of HI0 is discussed in light of these results.Proteins with properties similar or identical to those of the very lysine rich chromosomal protein Hi°have been described in several mammalian tissues and in tissue culture cells (1-16). The protein isolated from ox or mouse liver has been shown to consist of two subfractions that have identical molecular weights (25,000) but differ slightly in charge (2, 3). The two subfractions appear to have similar or identical amino acid compositions and peptide patterns. Recently it has been shown that Hi0 has extensive sequence homology with histone H5 from goose erythrocytes (4).Hi0 is of interest for several reasons. Its level in different tissues varies widely and it is predominantly found in tissues exhibiting little cellular proliferation (1,6,7,9,15,17). In earlier work, using indirect immunofluorescence with monospecific antibodies, we showed that Hi0 was present in many but not all fully mature postmitotic cells, and therefore that its distribution in different cells of the adult mouse is heterogeneous (15). These data suggest that Hi0 may play an important role in cell regulation.The concept that Hi0 is involved in developmental regulation is strengthened by the observations that in rat pancreas, liver, and spleen the protein appears after birth once cell proliferation in the organs has ceased (7,8,17). It has also been shown to decrease in regenerating rat pancreas and liver (5, 18).We report here studies on the regulation of Hi0 in developing mouse and in adult mouse and rat. The presence of Hi0 was shown to be correlated with cell maturation during development and liver regeneration. It was also found to be hormonally regulated in several glands in the adult. The results suggest that Hi0 may play a role in the maintenance of the mature differentiated state of some cells.MATERIALS AND METHODS Animals. Strain 129 male mice were used unless otherwise indicated. Fisher or Wistar male rats (both normal and hypophysectomized) were purchased from Iffa Credo (Paris, France). Hormones were injected either intraperitoneally or subcutaneously as described in the text or figure legends.Biochemical Methods. Lysine-rich histones were extracted from whole tissues with 5% perchloric acid as described (3). Proteins were analyzed by electrophoresis in polyacrylamide gels as described (10). After staining with Coomassie brilliant blue the gels were scanned at 590 nm and ...

Organization and expression of H1 histone and H1 replacement histone genes

“…The association of H1" gene expression and terminal cell differentiation [Panyim and Chalkley, 1969;Gjerset et al, 1982;Alonso et al, 1988;Cheng and Skovetchi, 19891 is reflected in a very complex promoter structure. In addition to the TATA box, the H1 box, and an Spl site (see above), the H1" promoter of mouse and man contains a binding site for the retinoic acid receptor [Breuer et al, 1989[Breuer et al, , 1993Bouterfa et al, in press] and other conserved sequence motifs within otherwise divergent promoter sequences.…”

Immunochemical analysis of the structure and function of chromosomal proteins

“…Histone H1° accumulates in the chromatin of terminally differentiated cells or in cells with a low rate of cell division (16). Chromosomal protein HMG-17 may be associated with chromatin regions which are in a transcribable conformation (14).…”

An Upstream Control Region Required for Inducible Transcription of the Mouse H1° Histone Gene during Terminal Differentiation

“…H1Њ was first detected in tissues exhibiting a low rate of cell division (56), and its accumulation can be induced in cultured cells upon growth inhibition (57). Conversely, the amount of H1Њ in the chromatin of quiescent cells is reduced upon resumption of proliferation, including during experimental liver and pancreas regeneration (29). Although the synthesis of H1Њ is not tissue specific, it is regulated during development.…”

“…Although the synthesis of H1Њ is not tissue specific, it is regulated during development. During prenatal development in the mouse, H1Њ is not readily detected in most cell types, notable exceptions being postmitotic lens fiber cells and primitive yolk sac-derived erythrocytes, which have highly condensed nuclei (29). However, after birth, H1Њ accumulates gradually in many tissues, and its levels in certain endocrine glands appear to depend on continuous hormonal stimulation (29).…”

“…During prenatal development in the mouse, H1Њ is not readily detected in most cell types, notable exceptions being postmitotic lens fiber cells and primitive yolk sac-derived erythrocytes, which have highly condensed nuclei (29). However, after birth, H1Њ accumulates gradually in many tissues, and its levels in certain endocrine glands appear to depend on continuous hormonal stimulation (29). H1Њ also accumulates in a number of cell culture lines undergoing terminal differentiation in vitro, including neuroblastoma (35,58), embryonal carcinoma (2), and melanoma (8,63) cell lines, myeloid leukemia cells (51), and mouse erythroleukemia (MEL) cell lines (11,42,55,67,73).…”