Heterochromatin and Euchromatin PDF

Heterochromatin and Euchromatin  Heterochromatin and Euchromatin Session Learning Outcomes (SLO) SLO# 1 : Describe how the packing of chromatin changes during the course of the cell cycle. SLO# 2 : Distinguish between heterochromatin and euchromatin. SLO# 3 : Describe the process of X in...

Heterochromatin and Euchromatin  Heterochromatin and Euchromatin Session Learning Outcomes (SLO) SLO# 1 : Describe how the packing of chromatin changes during the course of the cell cycle. SLO# 2 : Distinguish between heterochromatin and euchromatin. SLO# 3 : Describe the process of X inactivation in mammals and explain its function.  Chromosomes Interphase chromosome DNA is very dispersed so it can be accessed for replication and transcription. Mitotic chromosome DNA is in its most highly condensed state & favors delivery of an intact DNA package to each daughter cell.  Chromatin (Heterochromatin and Euchromatin) - Different forms of chromatin show different gene activity Heterochromatin Euchromatin chromatin that remains chromatin that returns to compacted during dispersed state after each interphase mitosis  Heterochromatin and Euchromatin Interphase chromosomes Heterochromatin Euchromatin Highly condensed areas Less compacted areas Inaccessible to Accessible to transcription enzymes transcription enzymes  Heterochromatin vs Euchromatin Heterochromatin Euchromatin - Stains darkly - Stains lightly - Repetitive sequences - Single copy sequences (genes) - Replicates later in the cell - Replicates early in the cell cycle cycle - DNA hypermethylated - DNA hypomethylated - Little or no recombination - Recombines -Transcriptionally repressive: - Transcriptionally active: silences gene expression permissive for gene expression - Localitazed to telomers and regions flanking centromers  Heterochromatin and Euchromatin – Heterochromatin divided into 2 classes depending on whether it's permanently or transiently compacted Facultative Constitutive heterochromatin heterochromatin specifically inactivated stays condensed in all cells at all times (certain phases of organism's life) permanently or (certain types of differentiated cells) silenced DNA  Heterochromatin Constitutive heterochromatin 1. In mammalian cells - most is found in regions flanking centromeres in a few other sites (Y chromosome distal arm in males). 2. In many plants, telomeres also consist of blocks of constitutive heterochromatin 3. Consists primarily of repeated DNA sequences & contains relatively few genes  Heterochromatin Constitutive heterochromatin 4. If normally active genes move into site adjacent to constitutive heterochromatin (change position via transposition or translocation) —> tend to become transcriptionally silenced (position effect). 5. May have components whose influence spreads out a certain distance, affecting nearby genes. 6. The spread of heterochromatin along a chromosome is normally blocked by specialized barrier sequences in genome  Heterochromatin Facultative heterochromatin example: X chromosome in mammals female Cells have 2 X Male cells have a chromosomes Y chromosome & X chromosome Two copies of most genes single copy of most genes carried on sex chromosomes carried on sex chromosomes only one X chromosome is transcriptionally active The other X chromosome is condensed as heterochromatic clump Barr body Heterochromatin Facultative heterochromatin Barr body Barr body ensures that cells of both males & females have the same number of active X chromosomes synthesize equivalent amounts of products encoded by X-linked genes  Heterochromatin Facultative heterochromatin X chromosome inactivation – The Lyon hypothesis: Heterochromatization inactivation of genes of X chromosome in female on that chromosome mammals occurs during early embryonic development Heterochromatin X chromosome inactivation-The Lyon hypothesis: Heterochromatized X chromosome is reactivated in germ cells before meiosis both X chromosomes are active during oogenesis all gametes get a euchromatic X chromosome  Heterochromatin X chromosome inactivation-The Lyon hypothesis: Heterochromatization in embryo is random process The paternally-derived & maternally-derived X chromosomes have equal chances of being inactivated in any given cell Once X chromosome is inactivated, same X chromosome is inactivated in all of the cell's descendants The consequences of X-inactivation Adult mammalian females are genetic mosaics (with different alleles functioning in different cells) paternal & maternal X chromosomes may have different alleles for same trait. X-linked pigment genes in cats are calico. Pigmentation genes in humans are not found on X chromosome so there are no calico women The Histone Code - Histones are subjected to a variety of post translational modifications (most often on the terminal tails) - Theses modifications are generated by specific enzymes that can add or remove chemical groups to or from amino acid residues in the histone tails. - Histones are acetylated and phosphorylated, altering their ability to bind to DNA. - These modifications can influence gene expression and other chromatin functions The Histone Code - The state & activity of a particular region of chromatin depends upon the specific modifications, or combination of modifications, to the histone tails in that region - The pattern of modifications on the tails of the core histones contains encoded information governing the properties of the nucleosomes containing them The Histone Code Two interrelated chromatin properties were shown to depend upon histone modification patterns: 1. The degree of compaction – most importantly, whether a region of chromatin is heterochromatic or euchromatic 2. The likelihood that a gene or cluster of genes will be transcribed Chemical modification of histone tails changes the shape of nucleosomes. When methyl, acetyl, or phosphate groups are attached to the tails, the tails change shape, altering access to the DNA wrapped around the core particle. In most cases, these modifications restrict access to the underlying DNA. Histone modification can silence DNA to form heterochromatin. Histone Post-translational Regulatory Modifications Covalent Modification of core histone tails: Acetylation of lysines (K), Mythylation of lysines, Phosphorylation of serines (S) Histone acetyl transferase (HAT) Histone deacetylase (HDAC) Histone Post-translational Regulatory Modifications  Transcriptional Regulation by Histone Modification Histone acetyltransferase is component of transcriptional activation complexes H1 Promotes Nucleosome Compaction H1Binds the complex. It inhibits new transcription Cause the creation Of new mRNA. H1 function thought to be regulated by phosphorylation on N and C terminal tails -H1 +H1  Modifications to histones and DNA direct formation of heterochromatin Deacetylation of H4 Methylation of CpG islands Methylation of H3 Position Effects on Gene Expression  Summary Chromosomes are decondensed during interphase and hard to visualize Gene expression needs the decondensation of chromosome loops Chromatin can be catagorized into heterocrhomatin and euchromatin depending on its activity Heterochromatin can be subdivided according to whether it is always inactive or only inactive some of the time Be familiar with the reasoning and consequences of X- inactivation The histone code hypothesis suggests that chemical modification of histone tails effects the activity regions of chromatin