Cohesinopathies, gene expression, and chromatin organization

  title={Cohesinopathies, gene expression, and chromatin organization},
  author={Tania Bose and Jennifer L. Gerton},
  journal={The Journal of Cell Biology},
  pages={201 - 210}
The cohesin protein complex is best known for its role in sister chromatid cohesion, which is crucial for accurate chromosome segregation. Mutations in cohesin proteins or their regulators have been associated with human diseases (termed cohesinopathies). The developmental defects observed in these diseases indicate a role for cohesin in gene regulation distinct from its role in chromosome segregation. In mammalian cells, cohesin stably interacts with specific chromosomal sites and colocalizes… 

Cohesin and human disease: lessons from mouse models.

Cohesin: a critical chromatin organizer in mammalian gene regulation.

The multifaceted functions of mammalian cohesins and their apparent functional hierarchy in the cell are discussed, with particular focus on their actions in gene regulation and their relevance to human developmental disorders.

Molecular Genetics of Cohesinopathies

The protein complex was given the name ‘cohesin’ because it was first characterised in sister chromatid cohesion during chromosome segregation, and is essential for correct chromosome segregation to daughter cells and to avoid aneuploidies and tumour formation.

The Cohesin Complex and Its Interplay with Non-Coding RNAs

This review provides a condensed overview about the architecture as well as the function of the cohesin complex and highlights its multifaceted interplay with both short and long non-coding RNAs.

Gene Regulation by Cohesin in Cancer: Is the Ring an Unexpected Party to Proliferation?

Evidence is reviewed supporting the idea that the gene regulation function of cohesin represents a previously unrecognized mechanism for the development of cancer.

Targeted Sister Chromatid Cohesion by Sir2

A protein-targeting assay developed and reported that the evolutionarily conserved Sir2 histone deacetylase, an essential silent chromatin component, was both necessary and sufficient for cohesion, defining a unique role for Sir2 in cohesion of silent Chromatin that is distinct from the enzyme's role as a hist one de acetylase.

Binding, sliding, and function of cohesin during transcriptional activation

This study demonstrates that sister chromatid cohesion and transcription are mutually compatible because cohesin complexes retain their function when mobilized by RNA polymerase, and this system to study the fate of cohesIn during transcription in yeast is described.

Cohesin and its Loading Factor NIPBL in Genetic Diseases

Insight is provided into the mechanisms of two cohesin–related developmental disorders, CdLS and FSHD, and may lead to development of new therapeutic strategies, including Nipbl recruitment resulting in further stimulation of rRNA transcription.

Cohesin recruits the Esco1 acetyltransferase genome wide to repress transcription and promote cohesion in somatic cells

Eco1 uses cohesin as both a substrate and a scaffold for coordinating multiple chromatin-based transactions in somatic cells as well as other aspects of chromosome structure and function, including the regulation of gene expression.



Cohesin mediates transcriptional insulation by CCCTC-binding factor

It is proposed that cohesin functions as a transcriptional insulator, and it is speculated that subtle deficiencies in this function contribute to ‘cohesinopathies’ such as Cornelia de Lange syndrome.

Cohesins form chromosomal cis-interactions at the developmentally regulated IFNG locus

It is shown that cohesin forms the topological and mechanistic basis for cell-type-specific long-range chromosomal interactions in cis at the developmentally regulated cytokine locus IFNG and is used not only for the purpose of sister chromatid cohesion, but also to dynamically define the spatial conformation of specific loci.

A Molecular Determinant for the Establishment of Sister Chromatid Cohesion

In budding yeast, the head domain of the Smc3p subunit of cohesin is acetylated by the Eco1p acetyltransferase at two evolutionarily conserved residues, promoting the chromatin-bound cohes in to tether sister chromatids.

Regulation of the Drosophila Enhancer of split and invected-engrailed Gene Complexes by Sister Chromatid Cohesion Proteins

It is shown that transcription is hypersensitive to cohesin levels in two exceptional cases where cohesIn and the E(z)-mediated histone methylation simultaneously coat the entire Enhancer of split and invected-engrailed gene complexes in cells derived from Drosophila central nervous system.

The Drosophila cohesin subunit Rad21 is a trithorax group (trxG) protein

It is shown that the Drosophila Rad21 protein is encoded by verthandi (vtd), a member of the trxG gene family that is also involved in regulating the hedgehog gene, thus implicating these proteins in transcription activation and/or elongation.

Regulators of the cohesin network.

A picture is emerging in which complex regulatory networks are capable of differential regulation of cohesion in various contexts, and regulation via effectors and posttranslational modifications are reviewed.

Sister chromatid cohesion: a simple concept with a complex reality.

The 45-nm ringlike architecture of soluble cohesin is compatible with dramatically different mechanisms for both chromatin binding and cohesion generation, and offers the potential to provide important insights into higher-order chromosome organization and chromosome biology.

Functional contribution of Pds5 to cohesin-mediated cohesion in human cells and Xenopus egg extracts

It is proposed that Pds5 proteins play both positive and negative roles in sister chromatid cohesion, possibly by directly modulating the dynamic interaction of cohesin with chromatin, which would explain why cells lacking PDS5 function display rather complex and diverse phenotypes in different organisms.

Cohesin Is Required for Higher-Order Chromatin Conformation at the Imprinted IGF2-H19 Locus

The data show that cohesin has a critical role in maintaining CTCF–mediated chromatin conformation at the IGF2-H19 locus and that disruption of this conformation coincides with changes in IGF2 expression, and it is proposed that Cohesin can mediate interactions between DNA molecules in cis to insulate genes through the formation of chromatin loops.