Recent advances in the spatial organization of the mammalian genome
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Ó Indian Academy of Sciences (0123456789().,-volV) (0123456789().,-volV)
Review Recent advances in the spatial organization of the mammalian genome YATENDRA KUMAR*, DIPTA SENGUPTA and WENDY A BICKMORE MRC Human Genetics Unit, IGMM, University of Edinburgh, Crewe Road South, Edinburgh EH42XU, UK *Corresponding author (Email, [email protected])
The mammalian genome is complex and presents a dynamic structural organization that reflects function. Organization of the genome inside the mammalian nucleus impacts all nuclear processes including but not limited to transcription, replication and repair, and in many biological contexts such as early development, differentiation and physiological adaptations. However, there is limited understating of how 3D organization of the mammalian genome regulates different nuclear processes. Recent advances in microscopy and a myriad of genomics methods—propelled by next-generation sequencing—have advanced our knowledge of genome organization to a great extent. In this review, we discuss nuclear compartments in general and recent advances in the understanding of how mammalian genome is organized in these compartments with an emphasis on dynamics at the nuclear periphery. Keywords. expression
Nucleus; TADs; LADs; DamID; Speckles; HDAC3; 3D genome; SAHFs; development; gene
1. Introduction The genetic material of eukaryotes is complex in form, function, dynamics and sheer size. A diploid human cell contains 6 billion base-pairs of DNA in the form of 23 pairs of chromosomes. The linear length of the unfolded DNA polymer accounts for * 2 m however this is accommodated inside the nucleus which is * 6 lm in diameter. This astonishing level of packaging is achieved in such a way that it does not impede replication, maintenance of and access to the genetic material. This complexity has driven biologists to explore structure of the nucleus and the way in which the genome is folded inside the nucleus. Chromatin is the physiological state of genetic material in the form of a nucleoprotein complex containing histone and non-histone proteins. Wrapping of the DNA polymer in
This article is part of the Topical Collection: Chromatin Biology and Epigenetics. http://www.ias.ac.in/jbiosci
the form of nucleosomes imparts the universal primary structure to chromatin which is akin to a ‘‘beads on a string’’ structure also known as the 11 nm fibre. The chromatin fiber is highly dynamic in its composition and physical properties which can be regulated by posttranslational modifications of histones, incorporation of variant histones and sequence-specific binding of various proteins involved in DNA replication, transcription and DNA damage repair (Cosgrove and Wolberger 2005). Visualization of densely packed heterochromatin and its preferential localization in the peripheral parts of the nucleus propelled the idea that chromatin inside the nucleus is spatially segregated and inspired the field of nuclear organization (Passarge 1979). It is now evident that chromatin organization is not only non-random
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