1.2 From static to dynamic

Chromotin dynamics

1. Cell Cycle

2. Inactive X Chromosome

3. Embryonic Stem Cell Differentiation

Although some aspects of the 3D genome architecture are conserved in different cell types, notable reorganization can happen in distinct biological processes and cell types. Dramatic changes may include mitosis process or X chromosome inactivation. Subtle changes may also important and may contribute to cell differentiation and reprogramming. Here we will introduce some cases that exemplify how dynamic changes influence the functions and formations.

3D Genome Reorganization During the Cell Cycle

Mitotic chromosomes are among the most recognizable structures in the cell, yet for over a century their internal organization remains largely unsolved. Naumova N et applied 3C, 5C and Hi-C techniques together and proposed mechanism about chromatin get condensed upon entering mitosis and how to reserve back in child cells. Here are few discoveries:

• In interphase: highly compartmentalized; cell type-specific organization. In metaphase: homogenous folding state that is locus-independent, common to all chromosomes, and consistent among cell types, suggesting a general principle of metaphase chromosome organization.

• At M phase, previously described features of interphase chromosome organization, such as TADs and compartments, appear to be completely erased.

• Mitotic chromosomes are folded in two steps：

  • First, linear compaction is achieved by the formation of stochastic arrays of consecutive loops (80–120 kb in size), probably through loop extrusion mediated by SMC complexes [1].

  • Second, axial compression occurs to form the cylindrical shape of a mitotic chromosome.

After mitosis, all the structures should be rapidly established to guarantee a proper function as the parent cells. This process may largely depend on specific bookmarks on the chromosomes. (A great figure summary of this process is here). More insights of cell-fate conformation alterations of chromosome could be even closely surveyed by single-cell Hi-C study [2].

3D Genome Organization of the Inactive X Chromosome

Homologous chromosomes other than the X chromosome have highly similar high-order chromatin structure: The active X chromosome (Xa) has TADs of regular size, whereas the inactive X chromosome (Xi) is partitioned into two large, contiguous domains, with a general absence of TADs. Similar Xi organization is conserved across the human, rhesus macaque, and mouse. The boundary of two large domains on Xi lies near the DXZ4 macro-satellite and its orthologs, which are bound by CTCF on Xi but not on Xa [3], [4], [5].

3D Genome Reorganization During Embryonic Stem Cell Differentiation

In human embryonic stem cells (hESCs), TADs serve as stable organizational units, TAD boundary positioning is largely unchanged when hESCs differentiate into four distinct early embryonic cell lineages. However, the inter- or intra- TAD interactions level are changed in concert with the transcription levels and epigenetic states [6].

Another study found tissue type–specific feature of genome organization termed FIREs (frequently interacting regions), which involve multiple partners in the neighborhood and represent local chromatin interaction hot spots [7].

Referrence

[1] Yu, Miao, and Bing Ren. "The Three-Dimensional Organization of Mammalian Genomes." Annual review of cell and developmental biology 33 (2017): 265-289.