Histone Acetylation, DNA Methylation and Epigenetics

Histone Acetylation

Acetylation of the lysine residues at the N terminus of histone proteins removes positive charges, thereby reducing the affinity between histones and DNA.  This makes RNA polymerase and transcription factors easier to access the promoter region.  Therefore, in most cases, histone acetylation enhances transcription while histone deacetylation represses transcription.

Figure 4-G-1.  Acetylation and deacetylation of the lysine residue.

Histone acetylation is catalyzed by histone acetyltransferases (HATs) and histone deacetylation is catalyzed by histone deacetylases (denoted by HDs or HDACs).  Several different forms of HATs and HDs have been identified.  Among them, CBP/p300 is probably the most important, since it can interact with numerous transcription regulators.

Review Articles:

Hyperacetylated Chromatin Domains: Lessons from Heterochromatin - J. Biol. Chem., 2005.

Class II Histone Deacetylases: from Sequence to Function, Regulation, and Clinical Implication - Mole. Cell. Biology, 2005.

Transcription regulation by histone methylation: interplay between different covalent modifications of the core histone tails - Genes and Development, 2001

Acetylation of Histones and Transcription-Related Factors  - Microbiology and Molecular Biology Reviews, 2000.

Linker histone binding and displacement: versatile mechanism for transcriptional regulation - FASEB J., 2000.

DNA Methylation

DNA methylation is the addition of a methyl group (CH₃) to the DNA's cytosine base. It may affect gene transcription through several different mechanisms (Illustration). The methylation pattern is heritable after cell division (Illustration). Therefore, DNA methylation plays an important role in cell differentiation during development.

Review Articles:

DNA Methylation - Blood, 1999.

DNA Methylation and Cancer - J. Clin. Oncology, 2004

Epigenetics

Epigenetics is the study of heritable changes in chromatin (e.g., DNA methylation) without involving the change in DNA sequences.

Review Articles:

The Epigenetic Face of Systemic Lupus Erythematosus - J. Immunology, 2006.

The emerging science of epigenomics - Hum. Mol. Genet., 2006.

Epigenetics (10+ articles) -  Hum. Mol. Genet., 2005.

DNA methylation patterns and epigenetic memory - Genes and Development, 2002.

Epigenetic gene silencing in cancer - J. Clinical Investigation, 2000.

Imprinting

• A view through the clouds of imprinting - FASEB J., 2001.
• Imprinting in the Germ Line - Stem Cells, 2001.
• The impact of genomic imprinting for neurobehavioral and developmental disorders - J. Clinical Investigation, 2000.
• Beckwith-Wiedemann syndrome: imprinting in clusters revisited - J. Clinical Investigation, 2000.

Chromatin Remodeling

Review Articles:

Lashings of DNA methylation, forkfuls of chromatin remodeling - Genes and Development, 2001.

ATP-dependent remodeling and acetylation as regulators of chromatin fluidity - Genes and Development, 1999.

ATP-Dependent Chromatin-Remodeling Complexes - Molecular and Cellular Biology, 2000.

Chromatin Remodeling and Leukemia: New Therapeutic Paradigms - Blood, 1999.