Chromatin structure and control of gene transcription

Description

Undergraduate BMS238 Cell and molecular biology (Chromosomes) Mind Map on Chromatin structure and control of gene transcription, created by Kristi Brogden on 08/16/2014.
Kristi Brogden
Mind Map by Kristi Brogden, updated more than 1 year ago
Kristi Brogden
Created by Kristi Brogden over 10 years ago
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Resource summary

Chromatin structure and control of gene transcription
  1. Diversity of covalent modifications on N-terminal tails of core histones
    1. The building blocks of chromatin are nucleosomes
      1. Nucleosomes can be covalently modified - these structural changes to chromatin affect gene transcription
        1. A variety of covalent modifications are added to core histones within chromatin
          1. A variety of histone modifying enzymes affect gene transcription in distinct ways
            1. Covalent modifications are added to the termini of lysine (& arginine) and serine side chains
              1. Acetylation of histones creates binding sites for transcriptional activation factors that contain a bromodomain
                1. Mapping of histone acetylation across individual genes and gene collections
                  1. Evidence that Histone Acetylation is associated primarily with transcriptionally active promoter sequences
                2. Methylation of core histones
                  1. can create binding sites for
                    1. (a) transcriptional repressors that contain a chromodomain
                      1. (b) transcription activators that contain a PHD zinc finger domain
                        1. - depending on the particular lysine amino acid residue modified
                      2. Histone Acetyltransferases (HATs) can modify many different lysine residues in core histones
                        1. histone methyltransferases (HMTs) exhibit exquisite site-specificities - “Histone Code” Writers
                          1. Thus: different Histone modifications are distinct elements of a transcriptional regulatory code
                            1. an epigenetic code that lies on top of the genetic code
                              1. governs when and where genetic information is expressed
                              2. The Polycomb Group of proteins (Polycomb Repressive Complexes; PRC) includes proteins that can generate or recognise repressive chromatin modifications – Histone Code Writers and Readers
                              3. Combinations of different Histone modifications may be “read” by different Histone Code Reader proteins
                                1. Histone Code Readers allow information integration that determines whether a gene is ON or OFF
                            2. Histone Code Readers and Code Writers can recruit each other!
                              1. these interactions can help to spread the histone code
                                1. with impacts on gene expression
                                2. A close functional relationship exists between DNA methylation and transcriptionally repressive histone methylation
                                  1. Transcriptionally inactive promoters are frequently rich in methylated CpG dinucleotides
                                    1. Addition of methyl groups to cytosine residues is mediated by DNA methyltransferases (DNMTs)
                                      1. The histone methyltransferase EZH2 (methylates H3 on K27) physically interacts with DNMTs and together these enzymes mutually reinforce each other’s effects
                                3. Genetic changes
                                  1. Genetic alterations to DNA sequence can permanently affect gene expression
                                    1. epigenetic changes to chromatin structure, although relatively stable, are reversible
                                      1. Epigenetic modifications facilitate stable changes to gene expression, which may persist for the life of a cell or organism, but they can be erased in the germ line
                                    2. How do transcription activator proteins work?
                                      1. Activator proteins typically induce combinations of these effects
                                      2. How do transcription repressor proteins work?
                                        1. X chromosome
                                          1. Mammalian X-chromosome Inactivation equalizes the levels of X-chromosome derived gene products in males and females
                                            1. One X chromosome copy is silenced in each somatic cell during early development of female embryo, i.e. Xp or Xm
                                              1. Initial selection of the chromosome for silencing is random
                                                1. The silencing decision is then propagated clonally i.e. all progeny of each cell in which the silencing decision was taken inherit the same silenced X chromosome, i.e. Xp or Xm
                                            2. Males, XY: 1 dose of X-linked genes
                                              1. Females, XX: 2 doses of X-linked genes
                                                1. X-chromosome inactivation: the case of the calico cat
                                                  1. XO orange allele
                                                    1. Xo black allele
                                                      1. Males:
                                                        1. XO Y: orange Xo Y: black
                                                        2. Females:
                                                          1. XO XO : orange Xo Xo: black XO Xo: calico
                                                          2. Calico cats are exclusively female
                                                            1. Calico cats are heterozygous for a mutation in an X-linked coat pigment gene
                                                              1. Face, neck, belly and feet are white because no pigment cells in these areas
                                                                1. Patches of orange and black because of random X-inactivation during early embryogenesis
                                                            2. Mechanism of X-inactivation
                                                              1. involves synthesis of a non-coding RNA (Xist) from the X-inactivation centre (XIC) on the chromosome destined for inactivation
                                                                1. Xist RNA binds to the X chromosome in cis and promotes chromatin condensation via a process that spreads away from from the XIC in both directions
                                                                  1. Xist RNA promotes the formation of silent chromatin by recruiting histone modifying enzymes and other Polycomb Group components, leading to the H3K27 and H3K9 methylation of core Histones in X chromosome chromatin
                                                                    1. The Polycomb proteins - Histone Code Writers and Readers – detect Xist transcripts on the X chromosome that is to be inactivated and cause its transcriptional silencing
                                                              2. The Barr Body
                                                                1. a highly condensed inactive X chromosome at the periphery of the nucleus of female somatic cells
                                                                  1. A limiting amount of an unknown autosomal activator is thought to maintain expression of the active X
                                                              3. Euchromatin and heterochromatin
                                                                1. Euchromatin
                                                                  1. contains transcriptionally active genes (and genes that are competent for transcriptional activation)
                                                                  2. Heterochromatin
                                                                    1. contains transcriptionally silent genes and repetitive DNA sequences.
                                                                    2. two functionally distinct types of chromatin in eukaryotic cells
                                                                      1. Position effects
                                                                        1. Abnormal rearrangments of euchromatin and heterochromatin cause Position Effects that affect the transcriptional activity of the euchromatic genes.
                                                                          1. Aberrant chromosomal rearrangements that place heterochromatin next to euchromatin can shut down euchromatic gene activity
                                                                          2. Chromosomal rearrangements that alter the chromatin environment around the White locus in Drosophila cause Position Effects, which influence eye pigmentation
                                                                            1. The transcription silencing property of heterochromatin spreads into euchromatin and shuts down euchromatic genes
                                                                              1. but not completely: Position Effect Variegation of gene expression
                                                                                1. occurs in all eukaryotes
                                                                                  1. reflects an intersection between genetics (mutation) and epigenetics (effects of chromatin structure on transcription)
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