Chromatin structure "DNA+CHROMOSOME"

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Chromatin structure "dna with histones "
and genes +regulation of transcription by chromatin structure
chromosome and cell cycle

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Chromatin structure "DNA+CHROMOSOME"

  1. 1. “From gene to genome from histon to chromosome” “Ghmkin hassan” ‫غمكين‬‫حسن‬ Chromatin structure 1 Damascus university –pharmacy faculty Department of biochemistry
  2. 2. Content • Genome, how we see it ? • Nucleosomes • Beads on string • Higher-order chromatin structure: 30nm 300nm 700nm “chromosome” • Interphase chromatin. • Heterochromatin 2
  3. 3. why? 3
  4. 4. Genome, how we see it ? 4
  5. 5. DNA Molecules are Highly Condensed in Chromosomes ……….……….……….………………..……….……….……….………………..……….……….……….………………..……….……….……….……………… ..……….……….……….………………..……….……….……….………………..……….……….……….………………..……….……….……….…………… …..……….……….……….………………..……….……….……….………………..……….……….……….………………..……….……….……….………… ……..……….……….……….………………..……….……….……….………………..……….……….……….………………..……….……….……….……… ………..……….……….……….………………..……….……….……….………………..……….……….……….………………..……….……….……….…… …………..……….……….……….………………..……….……….……….………………..……….……….……….………………..……….……….……….… ……………..……….……….……….………………..……….……….……….………………..……….……….……….………………..……….……….………. ………………..……….……….……….………………..……….……….……….………………..……….……….……….………………..……….……….…… ….………………..……….……….……….………………..……….……….……….………………..……….……….……….………………..……….……….… …….………………..……….……….……….………………..……….……….……….………………..……….……….……….………………..……….………. ……….………………..……….……….……….………………..……….……….……….………………..……….……….……….………………..……….…… ….……….………………..……….……….……….………………..……….……….……….………………..……….……….……….………………..……….… …….……….………………..……….……….……….………………..……….……….……….………………..……….……….……….………………..………. ……….……….………………..……….……….……….………………..……….……….……….………………..……….……….……….………………..…… ….……….……….………………..……….……….……….………………..……….……….……….………………..……….……….……….………………..… …….……….……….………………..……….……….……….………………..……….……….……….………………..……….……….……….……………….. ……….……….……….………………..……….……….……….………………..……….……….……….………………..……….……….……….……………… ..……….……….……….………………..……….……….……….………………..……….……….……….………………..……….……….……….…………… …..……….……….……….………………..……….……….……….………………..……….……….……….………………..……….……….……….………… ……..……….……….……….………………..……….……….……….………………..……….……….……….………………..……….……….……….……… ………..……….……….……….………………..……….……….……….………………..……….……….……….………………..……….……….……….…… …………..……….……….……….………………..……….……….……….………………..……….……….……….………………..……….……….……….… ……………..……….……….……….………………..……….……….……….………………..……….……….……….………………..……….……….………. ………………..……….……….……….……………….. 5
  6. 6. ……….……….……….………………..……….……….……….………………..……….……….……….………………..……….……….……….……………….. ……….……….……….………………..……….……….……….………………..……….……….……….………………..……….……….……….……………….. ……….……….……….………………..……….……….……….………………..……….……….……….………………..……….……….……….……………….. ……….……….……….………………..……….……….……….………………..……….……….……….………………..……….……….……….……………….. ……….……….……….………………..……….……….……….………………..……….……….……….………………..……….……….……….……………….. ……….……….……….………………..……….……….……….………………..……….……….……….………………..……….……….……….……………….. ……….……….……….………………..……….……….……….………………..……….……….……….………………..……….……….……….……………….. ……….……….……….………………..……….……….……….………………..……….……….……….………………..……….……….……….……………….. ……….……….……….………………..……….……….……….………………..……….……….……….………………..……….……….……….……………….. ……….……….……….………………..……….……….……….………………..……….……….……….………………..……….……….……….……………….. ……….……….……….………………..……….……….……….………………..……….……….……….………………..……….……….……….……………….. ……….……….……….………………..……….……….……….………………..……….……….……….………………..……….……….……….……………….. ……….……….……….………………..……….……….……….………………..……….……….……….………………..……….……….……….……………….. ……….……….……….………………..……….……….……….………………..……….……….……….………………..……….……….……….……………….. ……….……….……….………………..……….……….……….………………..……….……….……….………………..……….……….……….……………….. ……….……….……….………………..……….……….……….………………..……….……….……….………………..……….……….……….……………….. ……….……….……….………………..……….……….……….………………..……….……….……….………………..……….……….……….……………….. ……….……….……….………………..……….……….……….………………..……….……….……….………………..……….……….……….……………….. ……….……….……….………………..……….……….……….………………..……….……….……….………………..……….……….……….……………….. ……….……….……….………………..……….……….……….………………..……….……….……….………………..……….……….……….……………….. ……….……….……….………………..……….……….……….………………..……….……….……….………………..……….……….……….……………….. ……….……….……….………………..……….……….……….………………..……….……….……….………………..……….……….……….……………….. ……….……….……….………………..……….……….……….………………..……….……….……….………………..……….……….……….……………….. ……….……….……….………………..……….……….……….………………..……….……….……….………………..……….……….……….……………….. ……….……….……….………………..……….……….……….………………..……….……….……….………………..……….……….……….……………….. ……….……….……….………………..……….……….……….………………..……….……….……….………………..……….……….……….……………….. ……….……….……….………………..……….……….……….………………..……….……….……….………………..……….……….……….………………..6
  7. 7. 1/10,000 . 7
  8. 8. • Chromatin consists of: • Histones • Nonhistone proteins. • RNA (small amount). 8
  9. 9. Nucleosomes are a Basic Unit of chromosome Structure: 9
  10. 10. 10
  11. 11. Beads on string • Nucleosome positing ,sliding 10nm 11
  12. 12. Higher-order chromatin structure : • Chromatin fiber: Interphase and mitotic chromatin 30 nm:  zigzag model  solenoidal structure 12
  13. 13. solenoidal structure 13
  14. 14. Fifth H1/H5 14
  15. 15. Chromatin loops 15
  16. 16. 16
  17. 17. 17
  18. 18. final level 18
  19. 19. Interphase chromatin “Chromosome Territories” “nucleolar organizing regions” 19
  20. 20. 20
  21. 21. Chromosome kissing 21
  22. 22. Heterochromatin • Inactive Chromatine heterochromatin : a highly condensed form • Active Chromatin euchromatin. all the rest, which is less condensed 22
  23. 23. Constitutive heterochromatin: always condensed and thus inactive (found near centromers and telomers ). Facultative heterochromatin: at times condensed and at others Uncondensed and actively transcribed appearing as euchromatin (X chromosome) 23
  24. 24. Centromer & telomer 24
  25. 25. 25
  26. 26. How it form? • "Histone Code” : • The covalent modification of core histone tails • Histone Variants 26
  27. 27. 27
  28. 28. Histone Variants 28
  29. 29. Histon code • A Complex of Code-reader and Code-writer proteins 29
  30. 30. the majority of repetitive sequences are nongenic and, most serve no known function. We will explore three main categories of repetitive sequences: (1) heterochromatin found to be associated with centromeres and making up telomeres; (2) tandem repeats of both short and long DNA sequences; (3) transposable sequences that are interspersed throughout the genome of eukaryotes 30
  31. 31. Centromeric DNA Sequences what is Satellite DNA? In humans, one of the most recognized satellite DNA sequences is the alphoid family. Found mainly in the centromere regions, a 171- bp motif of alphoid DNA is present in tandem head-to-tail repeating arrays totaling up to 1 million base pairs. Embedded somewhere in this repetitive DNA are more specific sequences that are critical to centromere function. While such a motif is present in other closely related primates, neither the sequence nor the number of repeats of the human 171-bp sequence is conserved. highly repetitive DNA, which constitutes about 5 percent of the human genome 31
  32. 32. Middle Repetitive Sequences: VNTRs and STRs • variable number tandem repeats (VNTRs). These repeating DNA sequences may be 15 to 100 bp long and are found within and between genes. Many such clusters are dispersed throughout the genome, and they are often referred to as minisatellites. (ATTCCAGCCTTAACCG)n • Another group of tandemly repeated sequences consists of di-, tri-, tetra-, and pentanucleotides, also referred to as microsatellites or short tandem repeats (STRs). Like VNTRs, they are dispersed throughout the genome and vary among individuals in the number of repeats present at any site. For example, in humans, the most common microsatellite is the dinucleotide where n equals the number of repeats. Most commonly, n is between 5 and 50. These clusters have served as useful molecular markers for genome a (CA)n 32
  33. 33. Repetitive Transposed Sequences: SINEs and LINEs • interspersed individually throughout the genome, rather than being tandemly repeated. They can be either short or long, and many have the added distinction of being transposable sequences, which are mobile and can potentially move to different locations within the genome 33
  34. 34. • short interspersed elements, called SINEs, are less than 500 base pairs long and may be present 500,000 times or more in the human genome. Alu family (the name is based on the presence of DNA sequences recognized by the restriction endonuclease AluI). • long interspersed elements (LINEs) represents yet another category of repetitive transposable DNA sequences. LINEs are usually about 6 kb in length and in the human genome are present 850,000 times. The most prominent example in humans is the L1 family. SINEs and LINEs represent a significant portion of human DNA. SINEs constitute about 13 percent of the human genome, whereas LINEs constitute up to 21 percent.Within both types of elements, repeating sequences of DNA are present in combination with unique sequences. 34
  35. 35. Noncoding RNAs and Chromatin Structure 35
  36. 36. 36
  37. 37. • Genome, how we see it ? • Nucleosomes • Beads on string • Higher-order chromatin structure: 30nm 300nm 700nm “chromosome” • Interphase chromatin. • Heterochromatin 37 summary
  38. 38. 38

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