Gene

Function (biology)

Cell biology

Linguistics

Philosophy

Biology

Enhancer

Epigenetics

Transcription (linguistics)

Cell growth

Somatic cell

Regulation of gene expression

Demethylation

DNA demethylation

DNA methylation

Lineage (genetic)

Genetics

Methylation

Epigenetics of physical exercise

Transcription factor

5-Hydroxymethylcytosine

Conditional gene knockout

Cell

Psychological repression

Gene expression

Phenotype

Cellular differentiation

Proceedings of the National Academy of Sciences

There is ample evidence that somatic cell differentiation during development is accompanied by extensive DNA demethylation of specific sites that vary between cell types. Although the mechanism of this process has not yet been elucidated, it is likely to involve the conversion of 5mC to 5hmC by Tet enzymes. We show that a Tet2/Tet3 conditional knockout at early stages of B-cell development largely prevents lineage-specific programmed demethylation events. This lack of demethylation affects the expression of nearby B-cell lineage genes by impairing enhancer activity, thus causing defects in B-cell differentiation and function. Thus, tissue-specific DNA demethylation appears to be necessary for proper somatic cell development in vivo.

Tissue-specific DNA demethylation is required for proper B-cell differentiation and function