Chapter 1/Cytology and Organization of Cell Types complexes of proteins called transcription factors Each of these proteins possesses special DNA binding domains and requires direct contact with the dna to function. However the long stretch of DNA, which in humans measures about 3 cm long, is folded thousands of times to fit into a nucleus only a few micrometers in diameter. Such compaction cre- ates a potential problem for factors that must gain free access to corresponding binding sites and other regulatory regions on the DNA strand. Another group of proteins, called histones, packs the dNA so that it is folded, coiled, and compressed many times over to form fibers called chromatin visible as fine threads in the interphase nucleus(Fig. 2)and, in Fig. 2. Electron micrograph of a nucleus of a hypothalamic an even more contracted form, as chromosomes in neuron. The nucleus(N) is separated from the cytoplasm by a the dividing cell nuclearenvelope(NE). A conspicuous nucleolus(Nu)signifies In the mature neuron, the nucleus remains in int a great demand for ribosomal RNA by the neuron. Proteins phase. DNA is segregated into morphologically disti called histones associate with DNA to form chromatin, which areas, reflecting the degree of chromatin may appear extended (i.e, euchromatin) or condensed (i.e, which is a function of nuclear activity(Fig. 2).Riboso heterochromatin), depending on the translational activity of mal dNa genes and their products are separately fine fibers of euchromatin(asterisk). Heterochromatin(arrow- packed into a structurall y defined compartment heads) is seen as clumps within the nucleus, on the inner sur- called the nucleolus that is specialized for ribosomal face of the nuclear envelope, or associated with the nucleolus. RNA synthesis. Highly coiled regions for the genome appear as dense, irregularly shaped clumps known as heterochromatin. These areas of condensed chro- perturbations caused by cytoplasmic filaments. More- matin are situated within the nucleus along the inner over, it separates the process of RNA synthesis (i.e, nuclear membrane, in association with the nucleolus transcription)from that of protein synthesis (i. e, trans- or dispersed within the nucleus proper. Other regions lation). This segregation of function has an important of the genome readily available for transcription into advantage over the situation in prokaryotes, in which messenger RNA appear as fine filaments and are transcription and translation occur simultaneously. In known as euchromatin these organisms, protein synthesis begins before the completion of transcription, limiting the opportunity 2.1.1.1. Chromatin Remodeling in Behavior for modifying the RNA. Translation in eukaryotes and in Neural Diseases. The manner in which does not begin until the RNA is transported into the DNA encodes proteins is discussed elsewhere.These cytoplasm. In the nucleus, the RNa may be modified proteins ultimately affect our behavior.However in such a way that specific portions of the RNa mole- novel studies reveal the exciting possibility that our cule are removed (ie, RNA Splicing) or altered. These behavior may modify the genome and that some of complex changes have important implications for cell these changes may become permanent. These changes function. Mechanisms that control variability at the are known as environmental programming and are part level of transcribed rNa allow a single gene to code of the phenomenon of epigenesis, whereby stable and for several different proteins, resulting in the rich diver- heritable alterations in gene expression are not directly sity seen, especially in neurons, in the form of neuro- due to changes in DNA sequences. An example is that peptides, receptors, ion channels, and cytoskeletal of maternal behavior in rats. In rodents materna proteins behavior, such as tactile stimulation by the mother toward the pup, can result in increased amounts of 2.1.1 MATIN STRUCTURE IN THE REGULATION OF GENE ACTIVITY specific second messengers and gene transcription fac- tors. Binding of certain transcription factors to the The degree of complexity of gene expression is further DNA may result in the recruitment of a class of multiplied at another, even more fundamental level of enzymes, called histone acetyltransferases. These gene regulation: the DNA Genes are turned on by enzymes increase histone acetylation, which permitsperturbations caused by cytoplasmic filaments. More￾over, it separates the process of RNA synthesis (i.e., transcription) from that of protein synthesis (i.e., trans￾lation). This segregation of function has an important advantage over the situation in prokaryotes, in which transcription and translation occur simultaneously. In these organisms, protein synthesis begins before the completion of transcription, limiting the opportunity for modifying the RNA. Translation in eukaryotes does not begin until the RNA is transported into the cytoplasm. In the nucleus, the RNA may be modified in such a way that specific portions of the RNA mole￾cule are removed (i.e., RNA splicing) or altered. These complex changes have important implications for cell function. Mechanisms that control variability at the level of transcribed RNA allow a single gene to code for several different proteins, resulting in the rich diver￾sity seen, especially in neurons, in the form of neuro￾peptides, receptors, ion channels, and cytoskeletal proteins. 2.1.1. CHROMATIN STRUCTURE IN THE REGULATION OF GENE ACTIVITY The degree of complexity of gene expression is further multiplied at another, even more fundamental level of gene regulation: the DNA. Genes are turned on by complexes of proteins called transcription factors. Each of these proteins possesses special DNA￾binding domains and requires direct contact with the DNA to function. However, the long stretch of DNA, which in humans measures about 3 cm long, is folded thousands of times to fit into a nucleus only a few micrometers in diameter. Such compaction cre￾ates a potential problem for factors that must gain free access to corresponding binding sites and other regulatory regions on the DNA strand. Another group of proteins, called histones, packs the DNA so that it is folded, coiled, and compressed many times over to form fibers called chromatin, visible as fine threads in the interphase nucleus (Fig. 2) and, in an even more contracted form, as chromosomes in the dividing cell. In the mature neuron, the nucleus remains in inter￾phase. DNA is segregated into morphologically distinct areas, reflecting the degree of chromatin condensation, which is a function of nuclear activity (Fig. 2). Riboso￾mal DNA genes and their products are separately packed into a structurally defined compartment called the nucleolus that is specialized for ribosomal RNA synthesis. Highly coiled regions for the genome appear as dense, irregularly shaped clumps known as heterochromatin. These areas of condensed chro￾matin are situated within the nucleus along the inner nuclear membrane, in association with the nucleolus or dispersed within the nucleus proper. Other regions of the genome readily available for transcription into messenger RNA appear as fine filaments and are known as euchromatin. 2.1.1.1. Chromatin Remodeling in Behavior and in Neural Diseases. The manner in which DNA encodes proteins is discussed elsewhere. These proteins ultimately affect our behavior. However, novel studies reveal the exciting possibility that our behavior may modify the genome and that some of these changes may become permanent. These changes are known as environmental programming and are part of the phenomenon of epigenesis, whereby stable and heritable alterations in gene expression are not directly due to changes in DNA sequences. An example is that of maternal behavior in rats. In rodents, maternal behavior, such as tactile stimulation by the mother toward the pup, can result in increased amounts of specific second messengers and gene transcription fac￾tors. Binding of certain transcription factors to the DNA may result in the recruitment of a class of enzymes, called histone acetyltransferases. These enzymes increase histone acetylation, which permits Fig. 2. Electron micrograph of a nucleus of a hypothalamic neuron. The nucleus (N) is separated from the cytoplasm by a nuclear envelope (NE). A conspicuous nucleolus (Nu) signifies a great demand for ribosomal RNA by the neuron. Proteins called histones associate with DNA to form chromatin, which may appear extended (i.e., euchromatin) or condensed (i.e., heterochromatin), depending on the translational activity of specific regions of the genome. Most of the nucleus contains fine fibers of euchromatin (asterisk). Heterochromatin (arrow￾heads) is seen as clumps within the nucleus, on the inner sur￾face of the nuclear envelope, or associated with the nucleolus. Chapter 1 / Cytology and Organization of Cell Types 5