The H1 and core histone subtypes: differential gene expression and varied primary structures

Abstract

The patterns of chromosomal proteins reflect in many cases the functional state of the respective cell type. The H1 histone group is particularly important in this respect, since these histones are involved in the higher order chromatin organization above the level of chains of nucleosomes. In mammals, the H1 histone family comprises at least five main subtypes (H1a-H1e), a testicular variant (H1t) and, thirdly, a subtype H1(0), which is found only in terminally differentiated cells. The H1(0) variant is structurally related to the avian red blood cell specific histone H5, which was the basis for our recent isolation of the human H1(0) gene. Changes of H1 histone patterns may be crucial events in modulating local chromatin arrangements, since the formation of higher order chromatin structures depends on a cooperative interaction of the H1 histones. Variations in their patterns can be studied in vivo during several developmental processes (such as spermatogenesis, erythropoiesis, maturation of several cell types) or in vitro in several tumor cell lines upon treatment with several inducers or upon inhibition of cell division. The differential regulation of the individual H1 subtypes is reflected in the gene and mRNA structures coding for the respective proteins. The cell cycle regulated histones are mostly encoded by non-polyadenylated mRNAs, whereas H5 as well as H1(0) mRNA shows a poly(A) tail at its 3' end. In conclusion, gene activity may not only be controlled at the level of RNA polymerases and their regulatory transcription factors. The varied patterns of chromosomal proteins at different stages during development and differentiation suggest that the local or overall organization of chromatin plays an additional role in these regulatory programs. Hence, the analysis of variations in patterns of chromosomal proteins is an integral part of the investigation of gene regulation mechanisms.