Inheritance of Chromatin Structures

Although all somatic cells contain the same genetic information, the cells of the liver divide to form only liver cells, and skin cells divide into new skin cells. Each tissue type has specific chromatin packaging and histone modifications which result in distinct gene expression patterns.  These structural features of chromatin – such as the centromere, the heterochromatin, and  euchromatin regions – are epigenetically inherited, meaning their characteristics are passed from mother to daughter cell in addition to the genetic material.  This means that the tissue specific phenotypes of liver or skin or other specialized cells are passed on during each round of cell division without the necessity for changes to the genetic material.  De novo centromere formation on newly synthesized DNA begins with the binding of histone H3 variant CENP-A to the AT-rich satellite DNA to form centromere specific nucleosomes. Once initiated, the structure selectively recruits more CENP-A histones to its vicinity, in a cooperative manner.  During DNA replication, the histone octamer ahead of the replication fork is broken down into two H2A-H2B dimers and H3-H4 tetramer.  The two H2A-H2B dimers are completely removed from the octamer, whereas, the H3-H4 tetramers are loosely attached to the DNA and distributed randomly to daughter strands.  Newly synthesized H3-H4 tetramers are then added to both the strands to fill the spaces. This is followed by the addition of two H2A-H2B dimers – half which are the original molecules, and the other half are new – to complete the octamer.  In yeast, following DNA replication, acetylation of histone H3 in the newly synthesized strand marks the euchromatin, whereas deacetylation of H3 histone establishes the location of the compact chromatin domains, or heterochromatin.  Histone H3 methylation results in the condensation of chromatin. After DNA replication, the methylated histones are randomly distributed on the daughter strands, which then associate with the enzyme histone methyltransferase, to methylate the histone H3 on newly synthesized octamers.  X-chromosome inactivation is another example of the inheritance of chromatin structure. Female mammals receive two X-chromosomes, and males receive only one. In females, one of the X-chromosomes is inactivated, in a phenomenon called dosage compensation.  Here, a long non-coding RNA, XIST, initiates X inactivation by binding to the entire length of one X-chromosome in the embryonic stage. Subsequently, the chromosome is maintained in this inactive mode in successive cell divisions, through all somatic cells.