Cohen and pfaff access of another enzyme, demethylase, allowing along the envelope, the inner and outer membranes demethylation of a promoter to facilitate the recruit- are in continuity around the edges of each pore at a ment of DNA-binding proteins. These proteins, in region called the pore membrane( Fig. 3).The turn, may facilitate the expression of beneficial genes. nuclear pore is not a simple opening. The nuclear Conversely, in the absence of tactile stimulation and pore complex, itself, resembles a megaphone, with increased transcription factor, the promoter will the large opening facing the cytoplasm and the small remain methylated. An example of one of these pro- opening on the nuclear side. The basic structure moters is that for the glucocorticoid receptor, which consists of cytoplasmic fibrils, a central core, and a appears to be involved in modulating stress. Other nuclear cage or basket. Depending upon the organ behavioral studies suggest that handling of newborn ism, from 50 to 100 different proteins, called nucleo- rats decreases the extent of the hormonal response to porins, or Nups, make up the entire structure in adulthood; that is, the rats are less stressed as Irregardless of the organism, however, there are s. Importantly, the experience of tactile stimula- only about 30 distinct nucleoporins Nucleoporins tion by the mother may be converted into a phenotypic are involved in binding large transported molecules variation of the offspring that may be transmitted (displaying diameters of up to 39 nm), called cargo into human behavior, where the kind of parental care trapping the molecules, and terminating the trans- ort reaction. Other proteins, called ka received by children can impact physiologic responses (Kaps), are shuttling transport, or carrier, proteins to stress(resulting, for example, in cognitive and beha- Karyopherins, including importins and exportins viral problems)that persist into adulthood. Epige- recognize muclear localization or export signals on netic modifications can also result in various brain the cargo, which allow entry into or export from the dysfunctions, including Rubinstein-Taybi syndrome nucleus, respectively. The transport is energy and the Coffin-Lowry syndrome, disorders character ized by mental retardation, and the a-thalassemia mental retardation syndrome 2.1.2. NUCLEOLUS AS THE SITE OF RIBOSOMAL RNA A SYNTHESIS The nucleolus is a prominent spherical region of the nucleus(Fig. 2)containing that portion of the genome dedicated to the transcription of ribosomal DNA and the mechanisms for the assembly of ribo- somal subunits, the precursors of mature ribo- somes. Large precursor ribosomal RNA molecules are processed in the nucleus, resulting in the degra dation of almost half of the nucleotide sequences. B two subunits that are independently transported into the cytoplasm, where the mature ribosomes are assembled. The nucleolus is evident only in the interphase nucleus; in other cells that undergo mitosis, it decondenses, ribosomal RNA synthesis stops, and ribosomal DNA genes associate with specific regions of the chromosomes called nucleo- lar organizing regions 2.1.3. NUCLEAR PORE COMPLEX CONTROLS TRAFFIC Fig 3. Electron micrographs of nuclear pores.(A)The BETWEEN THE NUCLEUS AND CYTOPLASM pendicular section of the nuclear envelope(NE) shows the The double membrane comprising the nuclear continuity of the inner and outer nuclear membranes(arrow- heads) around a nuclear pore(arrow)of the nucleus(N).( B)A envelope presents a formidable barrier between the surface view shows the arrangement of nuclear pores in the nucleus and cytoplasm. Macromolecular traffic into nuclear membrane (NM). One of the nuclear pores(arron and out of the nucleus is achieved by perforations, head) shows the octagonal configuration of proteins compris or pores, in the nuclear envelope. At various points ing the nuclear pore complexaccess of another enzyme, demethylase, allowing demethylation of a promoter to facilitate the recruit￾ment of DNA-binding proteins. These proteins, in turn, may facilitate the expression of beneficial genes. Conversely, in the absence of tactile stimulation and increased transcription factor, the promoter will remain methylated. An example of one of these pro￾moters is that for the glucocorticoid receptor, which appears to be involved in modulating stress. Other behavioral studies suggest that handling of newborn rats decreases the extent of the hormonal response to stress in adulthood; that is, the rats are less stressed as adults. Importantly, the experience of tactile stimula￾tion by the mother may be converted into a phenotypic variation of the offspring that may be transmitted across generations. This phenomenon may translate into human behavior, where the kind of parental care received by children can impact physiologic responses to stress (resulting, for example, in cognitive and beha￾vioral problems) that persist into adulthood. Epige￾netic modifications can also result in various brain dysfunctions, including Rubinstein-Taybi syndrome and the Coffin-Lowry syndrome, disorders character￾ized by mental retardation, and the a-thalassemia/ mental retardation syndrome. 2.1.2. NUCLEOLUS AS THE SITE OF RIBOSOMAL RNA SYNTHESIS The nucleolus is a prominent spherical region of the nucleus (Fig. 2) containing that portion of the genome dedicated to the transcription of ribosomal DNA and the mechanisms for the assembly of ribo￾somal subunits, the precursors of mature ribo￾somes. Large precursor ribosomal RNA molecules are processed in the nucleus, resulting in the degra￾dation of almost half of the nucleotide sequences. The remaining ribonucleoprotein molecules form two subunits that are independently transported into the cytoplasm, where the mature ribosomes are assembled. The nucleolus is evident only in the interphase nucleus; in other cells that undergo mitosis, it decondenses, ribosomal RNA synthesis stops, and ribosomal DNA genes associate with specific regions of the chromosomes called nucleo￾lar organizing regions. 2.1.3. NUCLEAR PORE COMPLEX CONTROLS TRAFFIC BETWEEN THE NUCLEUS AND CYTOPLASM The double membrane comprising the nuclear envelope presents a formidable barrier between the nucleus and cytoplasm. Macromolecular traffic into and out of the nucleus is achieved by perforations, or pores, in the nuclear envelope. At various points along the envelope, the inner and outer membranes are in continuity around the edges of each pore at a region called the pore membrane (Fig. 3). The nuclear pore is not a simple opening. The nuclear pore complex, itself, resembles a megaphone, with the large opening facing the cytoplasm and the small opening on the nuclear side. The basic structure consists of cytoplasmic fibrils, a central core, and a nuclear cage or basket. Depending upon the organ￾ism, from 50 to 100 different proteins, called nucleo￾porins, or Nups, make up the entire structure. Irregardless of the organism, however, there are only about 30 distinct nucleoporins. Nucleoporins are involved in binding large transported molecules (displaying diameters of up to 39 nm), called cargo, trapping the molecules, and terminating the trans￾port reaction. Other proteins, called karyopherins (Kaps), are shuttling transport, or carrier, proteins. Karyopherins, including importins and exportins, recognize nuclear localization or export signals on the cargo, which allow entry into or export from the nucleus, respectively. The transport is energy Fig. 3. Electron micrographs of nuclear pores. (A) The per￾pendicular section of the nuclear envelope (NE) shows the continuity of the inner and outer nuclear membranes (arrow￾heads) around a nuclear pore (arrow) of the nucleus (N). (B) A surface view shows the arrangement of nuclear pores in the nuclear membrane (NM). One of the nuclear pores (arrow￾head) shows the octagonal configuration of proteins compris￾ing the nuclear pore complex. 6 Cohen and Pfaff