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Regulation

Chromatin remodeling - heterochromatin (telomers; Hox; etc)

Deacetilation of histones’ N-terminal binding to TATA box

(silencing) – lys +++ lig PO4 – mSin3

Histone modification – methylation, acetylation and phosphorilation

Reorganisation of nucleosomes – sliding along DNA, displacement,

spacing

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Competition between histones (nucleosome) and RNApol

Energy consuming factors for nucleosome reorganisation

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Linear DNA hampers ligation of FT; however, it is possible to

bind when sequence is on nucleossome surface

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Activators & Repressors

Repressors - 3 components: DNA binding subunit; corepressor and
Prot PcG do not repress but are responsible for maintenance of
histone deacetylase
repression (prot complex genes)

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Sens DNAseI

5’ - LCR

Resistence DNAseI; scs – specialised chromatin structures- isolate

genes (hsp70) from effects of surrounding regions

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Fab-7 essential for independent regulation iab6 & iab7

Insulators (Isoladores) – block transmission of activating or
inactivating signals effects in chromatin, e.g. prevent
heterochromatin expansion into regions

Between two insulators define a regulatory region; can be

directional
MARs (nuclear matrix); LCR

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Histone modification and transcription regulation

Histone modification (methylation)

Histone H3 – Lys4 – increasess

Acetylation - Lys9 – decreases (chromatin condensation)
- Lys 9 – required for DNA methylation
- Lys 79 – telomeric silencing
Phosphorylation (H3) – chromatin structure (activation);
mitosis

Lys 9 – acetylation – activation

Lys 14 – acetylation - prevents methylation of Lys 9
Methylation – depends of degree and site of methylation

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DNA methylation - citosine

CpG – methylated (++ repetitive regions)

CpG islands – methylated 5’ end genes – regulation

Methyltransferases
de novo Methylase
Maintenance or de novo
Post-replication (hemi-methylated)

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Imprinting

One gene (paternal or maternal) is switched off

Germline– reset then reprogramming

Imprinting results in expression patterns different from classical Mendelian

inheritance patterns
: both parents contribute equally to the genetic content
: imprinted genes contributed from the father and mother are not
equally expressed.

Maternally imprinted locus: mother is turned "off,“ father is turned "on."

(The opposite is true of a paternally imprinted gene)

5- methylcitidine (mC)
mCG – binds specific prot that interacts with mSin3, leading
to deacetylation - silencing

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X chromosome inactivation
X chromosome inactivation

1 – Usually paternal chromosome

- Gene dosage compensation

- Specific chromosome 2 – Cell division

- Transcription silencing 3 – Random inactivation

4 – Similar pattern for descendence/cell-line

Depending on cellular origin - mosaic

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X inactivation – genetics

X-inactivation center (XIC) (two non-translated RNAs: Xist and Tsix)

-Xist is the ONLY gene which is expressed from the Xi but not from the Xa

-Tsix RNA is transcribed antisense to Xist (negative regulator of Xist)

-high levels of DNA methylation, low levels of histone acetylation, low levels of
histone H3 lysine-4 methylation, and high levels of histone H3 lysine-9
methylation

-histone variant (macroH2A) is exclusively found on Xi nucleosomes

- Barr body – last duplicate; periphery nucleus;

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