Histology Wk 8 Flashcards
What does the nucleus consist of
Nuclear Envelope
● Chromatin
● Nucleolus
Nuclear envelope
The envelope has two concentric membranes separated by a narrow (30-50 nm) perinuclear space.
This space and the outer nuclear membrane are continuous with the extensive cytoplasmic network of the rough endoplasmic reticulum (RER).
Closely associated with the inner nuclear membrane is a highly organized meshwork of proteins called the nuclear lamina which stabilizes the nuclear envelope.Major components of this layer are the class of intermediate filament proteins called lamins that bind to membrane proteins and associate with chromatin in nondividing cells.
Nuclear envelope
The inner and outer nuclear membranes are bridged at nuclear pore complexes. Various core proteins of a nuclear pore complex, called nucleoporins, display eightfold symmetry around a lumen.
● Proteins to be imported have nuclear localization sequences. Such sequences bind specifically to transport proteins (importins) that in turn interact with proteins of the pore complexes for transfer across the nuclear envelope. Energy for the transport is derived from guanosine 5′-triphosphate (GTP), with specific GTPases helping provide directionality to the transfer.
Chromatin
Chromatin consists of DNA and all of the associated proteins involved in the organization and function of DNA.
● Humans, each cell’s chromatin (except that of eggs and sperm) is divided among 46 chromosomes (23 pairs).
● After DNA replication but before cell division, each chromosome consists of two identical chromatin units called chromatids held together by complexes of cohesin proteins.
Organization of chromatin
DNA must be extensively packaged within the nucleus. This occurs initially by the DNA associating with sets of small basic proteins called histones. The structural unit of DNA and histones is called the nucleosome, which has a core of eight histones (two copies each of histones H2A, H2B, H3, and H4), around which is wrapped about 150 bp of DNA. Each nucleosome also has a larger histone (H1) associated with both the wrapped DNA and the surface of the core. In the EM the series of nucleosomes on DNA resembles “beads on a string,” with 50-80 bp of linker DNA separating each bead. Nucleosomes are structurally dynamic; modification and rearrangement of the histones allows temporary unwrapping of the DNA and arrival of enzymes and other proteins required for replication and gene transcription.
● The 10-nm fiber of nucleosomes and DNA undergoes helical folding to yield a fiber with a diameter of 30 nm.
● Further packaging is not well understood.
● Many such loops appear tethered to central scaffold-like arrays containing large protein complexes
(condensins) capable of compacting chromatin.
● Further packaging during the first phase of cell division causes chromosomes to become visible as discrete
structures by light microscopy;
Components of a nucleosome
Core of 8 histone molecules:
H2A,H2B,H3,H4
H1 histone
Central dna
Link dna
DNA to chromatin
DNA- Nucleosomes (DNA and core histones)- packed nucleosomes in 30 nm fibre- extended loops of transcriptionally active chromatin, tethered to protein scaffold-condensed heterochromatin and dispersed euchromatin- entire chromosome at metphase
Microscopically two categories of chromatin can be distinguished in nuclei of most nondividing cells:
Euchromatin is visible as finely dispersed granular material in the electron microscope and as lightly stained basophilic areas in the light microscope.
Heterochromatin (Gr. heteros, other + chroma, color) appears as coarse, electron-dense material in the electron microscope and as intensely basophilic clumps in the light microscope.Heterochromatin tends to be concentrated near the nuclear lamina.
○ ○
Constitutive heterochromatin is generally similar in all cell types and contains mainly repetitive, gene-poor DNA sequences, including the large chromosomal regions called centromeres and telomeres, which are located near the middle (most often) and at the ends of chromosomes, respectively.
Facultative heterochromatin contains other regions of DNA with genes where transcription is variably inactivated in different cells by epigenetic mechanisms and can undergo reversible transitions from compact, transcriptionally silent states to more open, transcriptionally active conformations.Facultative heterochromatin also occurs in the small, dense “sex chromatin” or Barr body which is one of the two large X chromosomes present in human females but not males. The Barr body remains tightly coiled, while the other X chromosome is uncoiled, transcriptionally active, and not visible.
Karyotyping
Structures occupy discrete chromosomal territories within dispersed chromatin. Such studies show further that chromosomal domains with few genes form a layer beneath the nuclear envelope, while domains with many active genes are located deeper in the nucleus.
● Microscopic analysis of chromosomes usually begins with cultured cells arrested in mitotic metaphase by colchicine or other compounds that disrupt microtubules. After processing and staining the cells, the condensed chromosomes of one nucleus are photographed by light microscopy and rearranged digitally to produce a karyotype in which stained chromosomes can be analyzed.
Nucleolus
Generally spherical, highly basophilic subdomain of nuclei in cells actively engaged in protein synthesis.
● The intense basophilia of nucleoli is due not to heterochromatin but to the presence of densely concentrated ribosomal RNA (rRNA) that is transcribed, processed, and assembled into ribosomal subunits.
● Chromosomal regions with the genes for rRNA organize one or more nucleoli in cells requiring intense ribosome production for protein synthesis during growth or secretion.
Fibrillar and granular subunits
