Acidic Proteins of the Nucleus

348 Pages·1974·7.229 MB·English

by  Ivan Cameron (Eds.)

This is a volume in
CELL BIOLOGY
A series of monographs
Editors: D. E. Buetow, I. L. Cameron, and G. M. Padilla
A complete list of the books in this series appears at the end of the volume.
Acidic Proteins
of the Nucleus
Edited by
IVAN L. CAMERON
Department of Anatomy
University of Texas Health Science Center
at San Antonio
San Antonio, Texas
JAMES R. JETER, Jr.
McArdle Laboratory for Cancer Research
University of Wisconsin Medical Center
Madison, Wisconsin
ACADEMIC PRESS New York San Francisco London 1974
A Subsidiary of Harcourt Brace Jovanovich, Publishers
COPYRIGHT © 1974, BY ACADEMIC PRESS, INC.
ALL RIGHTS RESERVED.
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United Kingdom Edition published by
ACADEMIC PRESS, INC. (LONDON) LTD.
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Library of Congress Cataloging in Publication Data
Cameron, Ivan L
Acidic proteins of the nucleus.
(Cell biology series)
Includes bibliographies.
1. Nucleoproteins. 2. Cell nuclei. I. Jeter,
James R.Joint author. II. Title. [DNLM: 1. Cell
nucleus. 2. Cytology. 3. Proteins. QH595 A181]
QH595.C32 574.8'732 74-5691
ISBN 0-12-156930-6
PRINTED IN THE UNITED STATES OF AMERICA
List of Contributors
Numbers in parentheses indicate the pages on which the authors' contributions begin.
Vincent G. Allfrey ( 1 ), The Rockefeller University, New York, New
York
H. D. Betendes (191), Department of Genetics University of
Nijmegen, The Netherlands
Ivan L. Cameron (213), Department of Anatomy, University of
Texas Health Science Center at San Antonio, San Antonio,
Texas
Arthur Forer (159), Biology Department, York University, Downs-
view, Ontario, Canada
R. Stewart Gilmour (297), The Beatson Institute for Cancer Re-
search, Glasgow, Scotland
P. J. Helmsing (191), Department of Genetics, University of Nijme-
gen, The Netherlands
James R. Jeter, Jr. (213), McArdle Laboratory for Cancer Research,
University of Wisconsin Medical Center, Madison, Wisconsin
Lewis J. Kleinsmith (103), Department of Zoology, The University
of Michigan, Ann Arbor, Michigan
Wattace M. LeStourgeon (59, 159), Department of Molecular Biol-
ogy, Vanderbilt University, Nashville, Tennessee
ix
χ List of Contributors
Bruce E. Magun (137), Department of Anatomy, University of Ten-
nessee Medical Unit, Memphis, Tennessee
Gordhan L. Patel (29), Department of Zoology, University of
Georgia, Athens, Georgia
Thomas C. Spelsberg (247), Department of Endocrine Research,
Mayo Clinic, Rochester, Minnesota
Roger Totten (159), Department of Plant Pathology, Montana State
College, Bozeman, Montana
Wayne Wray (59), Department of Cell Biology, Baylor College of
Medicine, Texas Medical Center, Houston, Texas
Preface
The nucleus is the central repository of genetic information within
the cell, and this genetic information is encoded in a sequence of
deoxyribonucleotides. Each somatic cell nucleus of an organism con-
tains the same complete compliment of genetic material except in a
few clearly defined cases where some specific chromosomes are dis-
carded during somatic cell differentiation, as occurs in the gall
midge and in ascaris. It has become apparent that only a small part
of this total genetic information is expressed in any given cell at
any given time. How is the transcription of this genetic information
controlled? Many feel this to be the most exciting question in mod-
ern biology. This question has led many workers to suggest that
the nuclear proteins are the regulators of genetic expression in cells.
During the early 1940's Edgar and Ellen Stedman at Edinburgh
revived interest in the nucleoproteins, particularly the histones, as
possible repressors of specific chromosomal genes. Information con-
cerning the histones is nicely summarized in a series of monographs
(A. Kossal, "The Portamines and Histones," Longmans, Green and
Co., London, 1928; J. Bonner and P.O.P. Ts'o, eds., "The Nucleo-
histones," Holden-Day, San Francisco, 1964; H. Busch, "Histones
and Other Nuclear Proteins," Academic Press, New York, 1965;
D. M. P. Phillips, ed., "Histones and Nucleohistones," Plenum, Lon-
don, 1971; and L. S. Hnilica, "The Structure and Functions of His-
tones," The Chemical Rubber Co., Cleveland, 1972). Despite a
wealth of information on the chemistry and structure of histones it
has been disappointing to find that these proteins have only a
limited and nonspecific role in the regulation of genetic expression.
It also seems clear that this group of proteins has limited hetero-
geneity and has remained virtually unchanged during the evolution
of eukaryotic cells. Consequently, interest in the histones as specific
regulators of genetic expression has waned. More recently interest
has turned to the heterogeneous group of nucleoproteins which the
xi
xii Preface
Stedmans called "chromosomin." Recent workers refer to these
heterogeneous proteins as the nonhistone or the acidic nuclear pro-
teins, and it is felt by many that some of the proteins in this group
act as regulators of the expression of specific genes. It is now clear
that many of these proteins also play structural, enzymatic, mobility,
receptor, and probably other roles in the nucleus.
To strongly distinguish this group of nuclear proteins from the
histones we have chosen to refer to them as acidic nuclear proteins
rather than nonhistone nuclear proteins even though we feel, as do
most of the workers in the field, that these terms are equitable.
Historically these proteins were referred to as acidic in nature be-
cause they were insoluble in dilute mineral acids and their amino
acid composition showed a preponderance of acidic over basic
amino acid residues. However, isoelectric foscusing data have shown
that a few of these proteins are actually basic rather than acidic in
nature, therefore it is probably more correct to refer to the whole
group as nonhistone rather than acidic proteins.
Because of the large and growing interest in the acidic nuclear
proteins we decided that it would be worthwhile to bring to-
gether into one monograph the diverse and scattered information
on this topic. Although it seems of considerable value to collate
information in a rapidly growing field, we are only too aware that
this monograph is doomed to obsolescence. Nevertheless, we are
hopeful that the book will stand as a notable historical landmark
in the field.
This work gives a broad account of much of what is presently
known of the acidic nuclear proteins. Although some of the chapters
deal with various approaches for isolating, separating, and charac-
terizing these proteins, much of the book is directed toward eluci-
dating the functional role that these nuclear proteins may play in
differential gene expression. At present a variety of techniques is
used by many of the laboratories investigating these proteins. Tak-
ing into account the way the histone story developed we feel that
firm conclusions about the role of the acidic nuclear proteins will
not be possible until there are accepted standard high-resolution
techniques for the study of these proteins.
The contributors to this book are all active and eminent re-
searchers in their field. Each chapter contains some previously un-
published work and points the way to new and promising areas
Preface xiii
for future research. We feel that this monograph will serve as a
good reference background to the acidic nuclear proteins and will
stimulate researchers to unravel the exciting questions concerning
the role of these proteins.
Ivan L. Cameron
James R. Jeter, Jr.
I
DNA-Binding Proteins
and Transcriptional Control in
Prokaryotic and Eukaryotic Systems
VINCENT G. ALLFREY
I. Introduction 2
A. The Problem of Differential Transcription 2
B. Involvement of DNA-Associated Proteins 2
C. Histones and Chromatin Structure 2
II. Transcriptional Control in Prokaryotes—A Model for Higher
Organisms 3
A. The he Repressor 4
B. Repression of the hut Operons in Salmonella 6
C. The Lambda Repressor 7
D. Rho Factor—Geometry of the Functional Oligomers .. 8
Ε Positive Transcriptional Control by DNA-Binding Proteins 9
F. Low Molecular Weight RNA Initiation Proteins in E.
coli " 11
G. DNΑ-Unwinding Proteins 11
III. Transcriptional Control by Modification of RNA Polymerases ... 12
IV. Nuclear Nonhistone Proteins and Transcriptional Control in
Eukaryotes 13
A. Correlations with Gene Activity 13
B. Specificity in DNA-Binding by Nuclear Nonhistone
Proteins 15
C. Species-Selective DNA Binding 16
D. Sequence-Specific DNA Binding 17
E. Transcription of Unique and Repetitive DNA Sequences 20
F. Protein Phosphorylation and Gene Activation 21
References 21
ι
2 Vincent G. Allfrey
I. INTRODUCTION
A. The Problem of Differential Transcription
The process of cell differentiation, leading to the diversity of special-
ized cells in higher organisms, involves a selective transcription of
different regions of the total chromosomal DNA to produce the RNA pop-
ulations characteristic of different cell types. This selective, but partial
utilization of the genome occurs despite the presence in most diploid
somatic cells of a complete array of chromosomes and a DNA comple-
ment sufficient to specify the formation of an entire organism (1).
It is now clear that individual cells suppress the transcription of most
of their DNA (2) while they selectively activate a relatively small num-
ber of genes necessary for the synthesis, assembly, processing, and post-
synthetic modification of enzymes and structural proteins characteristic
of the cell type and the species. This is evident in the limited nature
of their RNA transcripts ( 2-4 ). In the course of embryonic development
and aging, different sets of genes are activated or repressed in response
to programmed signals from the nucleus, the cytoplasm, the cell mem-
brane, and the environment.
B. Involvement of DNA-Associated Proteins
The two aspects of transcriptional control—suppression of the template
activity of most of the DNA and activation of RNA synthesis at particular
genetic loci—require the participation of proteins associated with the
chromatin complex. These proteins influence the structure of the genetic
material, strengthen or weaken its interactions with RNA polymerases,
and transmit physiological control signals for gene activation or repres-
sion in response to hormones, cyclic nucleotides, and other types of
stimuli.
The main protein fractions concerned with structure and function
of chromatin include the histones—the basic suppressive components
of chromatin—and the more acidic nuclear proteins involved in positive
and selective aspects of genetic control.
C. Histones and Chromatin Structure
Speculations on the regulatory role of histones date back to Edgar
and Ellen Stedman who, in 1950, proposed that "the basic proteins of
cell nuclei are gene inhibitors, each histone or protamine being capable