OVERWIEW OF THREE DIMENSIONAL GENOM ORGANIZATION

Yıl 2019, , 208 - 216, 27.08.2019

Evrim Suna Arıkan Terzi , Müjgan Özdemir Erdoğan , Mustafa Solak

https://doi.org/10.18229/kocatepetip.450681

Öz

A fundamental property of genomes is their topological organization in the cell nucleus. “Chromosome territories” refer to the use of certain regions of the nucleus by a specific chromosomes. It is determined that, chromosomes are not arranged randomly in the cell space and many genes in the genom occupy preferred areas. The organization of chromosomal domains are associated to gene density and size. In this case, it has been reported that gene-rich chromosomes prefer interior positions and that gene-poor chromosomes prefer peripheral positions. Chromosomal domains are also dynamic structures, so genes can be displaced from the periphery to the interior position when opened.

It is known that the spatial organization of the human genome plays an important role in the transcriptional control of genes. Based on studies of promoter and enhancer interactions by DNA looping, it is clear that gene expression is facilitated and regulated through contacts of distal chromatin contacts. The primary research topics are how regulatory DNA elements and genes are wired to properly execute cell-specific transcription regulatory programs. Genetic experiments have uncovered three rules of enhancer–promoter engagement: linear proximity matters, enhancer and promoter compatibility and some sequences exist that can block enhancer activity. To understand the molecular mechanisms behind these rules, we need to know how regulatory sites exert activities over distance.

It is found that a given mammalian cell type contains thousands or more regulatory sites. With 200 different cell types, this confirms that our genome harbours a complex regulatory landscape. From linear DNA to the three dimensional nucleus, chromatin organization is well characterized on both the small scale and the very large scale; however, our understanding of the intermediate levels of chromatin organization remains limited. With the advent of chromosome conformation capture (3C) technologies tremendous progress in our understanding of three dimensional chromatin organization of interphase nucleus has been made.

In this review, it is mentioned about spatial organization of genom, some interactions in this organisation and some actual studies in recent years.

Anahtar Kelimeler

Three dimensional genome, Chromosome territories, Enhancer

ÜÇ BOYUTLU GENOM ORGANİZASYONUNA GENEL BAKIŞ

Öz

Genomların temel özelliği hücre çekirdeğindeki üç boyutlu topolojik organizasyonudur. “Kromozom alanları” terimi nükleusun belli bölgelerinin belli kromozomlar tarafından kullanılmasını ifade etmektedir. Yani kromozomların nüklear boşlukta rastgele düzenlenmediği, genom içindeki bazı genlerin tercih ettikleri bölgeleri işgal ettikleri tespit edilmiştir. Kromozom alanlarının organizasyonu gen yoğunluğu ve boyutu ile ilişkilidir. Bu durumda gen bakımından zengin kromozomların interior pozisyonları, gen bakımından zayıf kromozomların perifer pozisyonları tercih ettiği rapor edilmiştir. Kromozom alanları ayrıca dinamik yapılardır böylece genler açılacağı zaman periferden interior pozisyona doğru yer değiştirebilirler.

İnsan genomunun mekansal organizasyonunun genlerin transkripsiyonel kontrolünde önemli bir rol oynadığı bilinmektedir. DNA ilmeklenmesiyle promotör ve enhansır etkileşimleri temelli çalışmalar gen ekspresyonunun uzaktaki kromatin temaslarıyla düzenlendiğini göstermiştir. Düzenleyici DNA elemanları ve genlerin hücreye spesifik transkripsiyon düzenleyici programları nasıl yürüttüğü başta gelen araştırma konularındandır. Genetik çalışmalar enhansır promotör birlikteliğinin üç kuralı etrafında tamamlanır: Doğrusal yakınlık durumları, enhansır promotör uyumu ve enhansır aktivitesini bloklayabilen sekansların varlığı. Bu kuralların arkasında yatan moleküler mekanizmaları anlamak için regülatör bölgelerin uzak mesafelerde nasıl faaliyet gösterdiğini bilmeye ihtiyacımız vardır.

Herhangi bir hücre tipinin binlerce ya da daha fazla düzenleyici bölge içerdiği bulunmuştur. 200 hücre tipi göz önüne alındığında insan genomunun karmaşık bir düzenleyici sistem olarak çalıştığı görülmektedir. Doğrusal DNA’dan üç boyutlu nükleusa kadar kromatin organizasyonu küçük ve büyük ölçekte çok iyi karakterize edilmiştir ancak ara seviyelerdeki kromatin organizasyonu hakkında bilgilerimiz hala sınırlıdır. Kromozom konformasyonunu yakalama (3C) teknolojilerinin gelişmesi interfaz nükleusunun üç boyutlu kromatin organizasyonuna yeni bakış açısı getirmiştir.

Bu derlemede, genomun mekânsal organizasyonundan, bu organizasyondaki bazı etkileşimlerden ve son yıllarda yapılan bazı çalışmalardan bahsedilmiştir.

Anahtar Kelimeler

3D genom, Kromozom alanları, Enhansır, İzolatör

Kaynakça

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