Chromosomal Nonhistone Protein

Volume I: Biology

L. S. Hnilica

• Publisher: CRC Press
• Year: 2019
• Print ISBN:
  9781315891576
• eBook ISBN:
  9781351087575
• Topic: Biological Sciences
• Subtopic: Biology
• Index: Biological Sciences

The first volume of the Chromosomal Nonhistone Proteins treatise presents a summary of the many attempts in the literature to correlate changes in chromosomal histone proteins specificity and metabolism with transcriptional regulations in eukaryotic cells.

Chapter 1

NUCLEAR PROTEINS IN DIFFERENTIATION AND EMBRYOGENESIS

Warren Schmidt

TABLE OF CONTENTS

I.In troduction

II.The Histones

III.The Non histones

A.Qualitative and Quantitative Variations in NHCP

B.Tissue and Cell Specificity

IV.Conclusions

Acknowledgment

Reference

I. INTRODUCTION

The ordered progression of events which transform the pluripotent cells of the implanting blastocyst into the diversity of cell types characterisic of the complete organism can be justly referred to as one of the fundamental enigmas of biology. This series of processes, collectively referred to as cellular differentiation, is operationally defined as the progressive and selective manifestation of specialized functions and phenotypes particular to each cell type of a given organism. This definition is of course very inclusive and contains aspects of nearly all cellular processes, normal growth, and neoplasia. In this review the discussion will be restricted for the most part to development and embryogenesis of nonneoplastic cells.

It is important to remember that cellular differentiation ensues in general without a quantitative change in the DNA of the genome. The constancy of DNA among diploid cells of the same organism was demonstrated originally in the classical studies of Boivin et al.¹ and Mirsky and Ris² in the latter half of the 1940s. The concept has since been vindicated with a variety of studies including the elegant transplantation experiments of Gurdon³,⁴ and further on a molecular level with the original DNA-DNA reassociation studies of McCarthy and Hoyer.⁵ It is apparent that the genetic control of cellular differentiation cannot be explained easily through selective losses of nontranscribed portions of the genome. Moreover, only minor fractions of the genome in differentiated cells are actually represented in functional mRNA. Quite simply, only the expression of specific DNA segments is controlled during differentiation and the process likely depends upon selective gene activation, i.e., events occurring at the transcriptional and/or translational level.

It is generally believed that the model of genetic expression proposed by Jacob and Monod,⁶ will hold for eukaryotic cell regulation, that is, that the genome may be repressed or derepressed by regulatory molecules acting on DNA and either inhibiting or allowing transcription. Although the exact nature of these regulatory molecules remains to be identified in eukaryotic cells, an increasing amount of evidence indicates the nuclear proteins to fulfill at least a part of this role. Thus, if differentiation involves changes in the genetic expression of cells, we might ask ourselves what type of alterations can be observed in the nuclear proteins in part responsible for and accompanying genetic expression during cellular differentiation?

Chromatin is composed chiefly of DNA, a lesser quantity of RNA, and in general two classes of nuclear protein, the histones and nonhistones. In this review attention is focused mainly on the nonhistones and the histones will be only examined briefly since an increasing body of evidence indicates these proteins to fulfill mainly a structural role in the nucleus. It is also important to keep in mind that chromatin is defined operationally by the method used in its preparation. A number of nuclear protein fractions, some likely important in cellular differentiation, may be either enriched or diminished depending on the method of chromatin isolation.

II. THE HISTONES

Of the two main categories of nuclear proteins the histones are by far the most well characterized.⁷,⁸ They are small (mol wt about 20,000), metabolically stable, and highly basic polypeptides. Five principal classes have been detected throughout the plant and animal kingdoms, (H1, H2A, H2B, H3, and H4) and in a few instances an additional distinct species has been identified (e.g., H5 in avian erythrocytes).

One is impressed with the evolutionary conservation of the amino acid sequences of the histones, especially the arginine-rich fractions. Only two amino acid residues differ between histones H4 of pea bud or calf thymus.⁹ On the other hand, H1 histones (lysine-rich), are an exception to this evolutionary conservation. These fractions are heterogeneous, with species and tissue specificity being observed for their amino acid sequences and immunological properties.⁷,⁸,¹⁰,¹¹ As a class however, the evolutionary stability of histones suggests that they would be poor choices as regulatory molecules in cellular differentiation, but that they fulfill a common but highly important structural role in chromatin — one that would tend to protect the proteins from mutational variability.

Although quantitative levels of histones vary during early embryogenesis and differentiation, the same protein species in all cell types are observed from the gastrula stage onward.^12-15 The tight coupling of histone and DNA synthesis in the division cycle of a typical eukaryotic cell is not apparent in all animal embryos. In early cleavage stages of Xenopus embryos, histone synthesis is rapid and exceeds DNA synthesis manifold. However, DNA synthesis increases at a greater rate during the early hours postfertilization such that synthesis of both DNA and histone is nearly equivalent by 5 to 6 hr. Thereafter, DNA synthesis increases creating a subsequent deficit of histone which is apparently equivalented with the amount of DNA by a pool of histone made previously during oogenesis.¹⁶,¹⁷ It is unclear at the present what aspects of the amphibian pattern of histone synthesis applies to other groups of animals, however the uncoupling of DNA and histone synthesis during early embryogenesis in Xenopus poses interesting questions for chromatin assembly, replication, and cell division.

Some of the earliest studies performed on transcriptional regulation in eukaryotic cells indicated that histones are potent repressor molecules of DNA-dependent RNA synthesis,^18-20 but that the repression is generally nonspecific.^21-23 The limited heterogeneity of histones makes it unlikely that the molecules by themselves can recognize specific gene loci. Possibilities exist, however, that posttranslational modifications, i.e., phosphorylation, acetylation, and methylation may confer to histones greater specificity on gene repression through alterations of histone-histone, histone-DNA, or histone-nonhistone interactions. These modifications have been associated with changes in the transcriptional and structural properties of chromatin and have been observed during cellular development, differentiation, transformation with viruses, and hormonal stimulation.⁷,⁸,¹⁴ Posttranslational modifications of all nuclear proteins have the potential for produ...

Table of contents

• Cover
• Title Page
• Copyright Page
• Introduction
• The Editor
• Contributors
• Table of Contents
• Chapter 1 Nuclear Proteins in Differentiation and Embryogenesis
• Chapter 2 DNA-Binding Nonhistone Proteins
• Chapter 3 Role of Nonhistone Chromatin Proteins and Specific DNA Sequences in the Nuclear Binding of Steroid Receptors
• Chapter 4 Chemical Carcinogenesis
• Chapter 5 Nonhistone Proteins in Genetic Regulation
• Index