Biochemical Features of Nuclear Chromosomes Flashcards
Describe some key components that determine their structure & function
Describe chromatin in both of its states
Chromatin is made up of DNA, protein, and RNA. In metaphase, the chromatin is highly condensed. In interphase, the chromatin is either euchromatin or heterochromatin. Heterochromatin is highly condensed and stains darkly, transcriptionally inactive, AT rich, gene deficient. Euchromatin is loosely condensed, stains lightly, and transcriptionally active due to being accessible by transcription factors, GC rich, and has regions containing alot of genes.
What are the different states of heterochromatin and how do they relate to the structure of the chromosome?
Constitutive heterochromatin - almost always heterochromatic, centromeric and telomeric regions of the chromosome.
Facultative heterochromatin - a region of chromatin that is heterochromatic in one cell type and euchromatic in another.
How are housekeeping genes and tissue specific genes different in terms of their chromatin structure?
Housekeeping genes are essential to life and hence are chromatic in all cell types. Tissue specific genes are only euchromatic in the appropriate cell type. This demonstrates that not all genes (bar housekeeping) are needed in all cells at all times.
Describe the organisation of histones
Nuclear DNA wraps around histone octamers to form nucleosomes. This gives rise to the “beads on a string” structure. This structure gives rise to higher order folding that allows the DNA to be condensed up to 10,000x.
Describe the epigentic processes that control the condensation of chromatin
Condensation controlled by post-translational modification of N-terminal histone tails. Acetylation and phosphorylation remove the positive charge from the nucleosome and make it repel the negative DNA backbone, causing the chromatin to be loose and accessible. Methylation of histones increases the hydrophobicity and causes condensation of the chromatin. Also, methylation of the DNA itself on CpG dinucleotides leads to the silencing of genes. Histone protein variants such as H2AX phosphorylates nucleosomes at double strand break sites to mark DNA damage and facilitate chromatin remodelling and DNA repair.
Describe and explain the role of Cohesin
Cohesin ensures that the sister chromatids are attached during mitosis, until anaphase where it degrades and allows the chromatids to separate. Cohesin either links the chromatin via a simple embrace - one ring of cohesin around two sister chromatids or via a handcuff link, which is two interlocking rings of cohesin each around a chromatid. After condensation cohesin only links chromatids at the centromere. `
Describe and explain the role of condensin.
Has a role in chromatin condensation. Condensin I and II form an extrusion complex (two rings next to eachother) and DNA runs through the rings to form a loop, the length of which is determined by interactions with transcription repressor CTCF. This loop mechanism brings together sequences which are far apart - it may explain how different regions of the DNA adopt different condensation states in different parts of the nucleus.
Explain X chromosome inactivation
ncRNA can regulate gene expression - small ncRNA do this by degrading mRNA. Most dramatic example of lncRNA gene regulation is X chromosome inactivation by Xist. In females, one out of the two X chromosomes is inactivated and hence heterochromatic. It appears as a dark spot towards the periphery of the nucleus and it’s called the Barr body. Due to its heterchromatic nature it is strongly detected by antibodies for methylation. The Xist RNA acts on the chromosome it is transcribed from - acts in cis. The transcription is random. Xist binds to promoters of histone methylation and deacetylation. The progeny of the cell with the maternal X inactivated will all have the maternal X inactivated, but in tissues and between tissues this differs - leading to mosaicism.
