Epigenetics is the change made in gene expression without change in DNA sequences. It is reversible change without mutation. It is heritable both mitotically and meiotically.
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Primary mechanism of epigenetic changes:
- DNA methylation
- Post translational modification of Histone
- Non coding RNA
DNA methylation
It is adding methyl group in DNA. It changes the expression of DNA without changing the underlying sequence. While DNA is negatively charged, adding positive charge of methyl group attract each other and DNA gets inactivated or less activated. Also methylation in gene promoter silences gene transcription. DNA methylation has important role in genomic imprinting, lionization, ageing, carcinogenesis, Fragile X syndrome. DNA methylation can be detected by sodium bisulfide method.
Post translational modification of Histone
Post translational modification is adding or modifying chemical groups on a histone, altering its function, activity, localization and stability.
- Histone methylation: Adding positively charged methyl group (CH3 +) on positively charged histone protein creates high attraction with negatively charged DNA resulting in tightened DNA coiling, thus resulting in decreased transcription. It is usually reversible and sometimes it can cause activation of DNA depending upon location.
- Histone acetylation: Adding negatively charged acetyl group (CH3COO–) on positively charged histone protein creates removal of positive charge of histone resulting in relaxed DNA coiling, thus resulting in increased transcription.
- Histone deacetylation: Removal of negatively charged acetyl group (CH3COO–) leads to tightened DNA coiling resulting in decreased transcription. In Huntington disease, histone deacetylation may be responsible for transcriptional dysregulation and altered gene expression.
Other post translational modification of histone: histone phosphorylation, histone ADP ribosylation, histone monoubiquitination, histone sumoylation.
Non coding RNA
Micro RNA (mi-RNA)
Micro RNA blocks translation of mRNA. These are produced as hairpin structures by cell. It is synthesize by transcription of primary mi-RNA gene via RNA polymerase II enzyme. Thus produced primary mi-RNA is converted to pre mi-RNA dicer via Drosha nuclease (Class 2 ribonuclease III enzyme) or Pasha nuclease. The pre mi-RNA dicer escapes nucleus and forms mi-RNA duplex with expotin-5. One strand of mi-RNA duplex is responsible for formation of RNA induced silencing complex (RISC), which binds to target mRNA and suppresses it.
Abnormal expression of mi-RNA causes certain malignancies by silencing mRNA from a tumor suppressor gene. Example: B cell lymphoma.
Small interfering RNA (si-RNA)
It is derived from exogenous dsRNA source like virus and exhibits property of binding anywhere in target RNA. It is used in silencing the expression of a specific gene.
References:
- Harper’s Illustrated Biochemistry Thirty Second Edition.
- Lippincott’s Illustrated Reviews – Biochemistry.
- Robbins And Cotran Pathologic Basis Of Disease, 10th edition.
