In simpler organisms like bacteria, the majority of DNA is coding, while in more complex organisms, such as humans, a large part of the genome consists of non-coding sequences
Euchromatin appears as a loosely packed form of DNA, which is transcriptionally active, allowing genes to be transcribed into RNA
When observed under electron micrographs, euchromatin isolated from an interphase nucleus appears as a quasi-regular thread, approximately 30 nm thick
Upon partial unpacking in low salt conditions, the chromatin's "beads on a string" structure becomes evident, a phenomenon first observed in 1974. This refers to nucleosomes connected by linker DNA
Histones H3 and H4 can interact to form a dimer, and two H3-H4 dimers interact to form a tetramer. H2A-H2B dimers can then bind to this tetramer to form the full nucleosome
In vitro Nucleosome and Chromatin Structure Analysis
Through in vitro reconstitution, crystal structures of nucleosomes have been obtained, providing detailed insights into the organization of DNA and histones
The addition of the H1 histone, or linker histone, to the "beads on a string" form of chromatin, can lead to the formation of a more compact 30 nm fiber, a step in further DNA compaction
DNA compaction increases from the "beads on a string" structure (11 nm fiber) to a 30 nm fiber, and further to higher-order structures like extended chromatin (300 nm), compacted chromatin (700 nm), and ultimately metaphase chromosomes (1400 nm)
During mitosis, DNA is highly compacted into chromosomes, which are much shorter than the extended length of DNA
Sperm DNA is even more densely packed than typical chromatin, primarily using protamines instead of histones
Chromosomes occupy distinct domains within the interphase nucleus, allowing for regulated access to DNA for transcription and replication
The presence of nucleosomes and histones poses questions about how transcription can occur without obstruction and whether histones interfere with DNA replication
Histones can be modified in various ways, not only by acetylation or methylation but also by phosphorylation, ubiquitination, and other chemical modifications
Each modification can influence different outcomes in DNA-related processes, such as transcription, replication, and repair
1. Initiation involves the formation of a pre-replicative complex (pre-RC) at origins, which includes ORC (Origin Recognition Complex), Cdc6, Cdt1, and Mcm helicases
2. In S phase, the pre-RC is activated, allowing the recruitment of DNA polymerases and other replication factors
3. As DNA unwinds, parental histones are partially retained while new histones are added. NAP-1 and CAF-1 chaperone new histones to ensure proper nucleosome assembly
H3-H4 tetramers are likely retained and reassembled onto new DNA, while H2A-H2B dimers are displaced and replaced
New histones are synthesized, acetylated to maintain an open chromatin structure, and then incorporated into nucleosomes
After replication, new histones undergo modifications to replicate the epigenetic state of the parental chromatin, ensuring that daughter cells maintain the same gene expression patterns
DNA Methylation and Histone Modification interplay to regulate gene expression, typically silencing genes through chromatin condensation
Both histone modifications and DNA methylation are crucial for passing on epigenetic information to daughter cells, influencing traits and susceptibility to conditions
Studies indicate environmental conditions (like diet and stress) experienced by parents can influence gene expression patterns in offspring through epigenetic mechanisms