Structural and developmental dynamics of Matrix associated regions in Drosophila melanogaster genome

Abstract

Background Eukaryotic genome is compartmentalized into structural and functional domains. One of the concepts of higher order organization of chromatin posits that the DNA is organized in constrained loops that behave as independent functional domains. Nuclear Matrix (NuMat), a ribo-proteinaceous nucleoskeleton, provides the structural basis for this organization. DNA sequences located at base of the loops are known as the Matrix Attachment Regions (MARs). NuMat relates to multiple nuclear processes and is partly cell type specific in composition. It is a biochemically defined structure and several protocols have been used to isolate the NuMat where some of the steps have been critically evaluated. These sequences play an important role in genomic organization it is imperative to know their dynamics during development and differentiation. Results Here we look into the dynamics of MARs when the preparation process is varied and during embryonic development of D. melanogaster. A subset of MARs termed as “Core-MARs” present abundantly in pericentromeric heterochromatin, are constant unalterable anchor points as they associate with NuMat through embryonic development and are independent of the isolation procedure. Euchromatic MARs are dynamic and reflect the transcriptomic profile of the cell. New MARs are generated by nuclear stabilization, and during development, mostly at paused RNA polymerase II promoters. Paused Pol II MARs depend on RNA transcripts for NuMat association. Conclusions Our data reveals the role of MARs in functionally dynamic nucleus and contributes to the current understanding of nuclear architecture in genomic context.

Transposable elements as scaffold/matrix attachment regions: shaping organization and functions in genomes

“…Both methods of extraction uncover interactions that are the components of the same network, validating either the low-salt (LIS) or high-salt (NaCl) method as good enough to isolate S/MARs ( Linnemann et al, 2009 ). Another recent study found that interventions like heat stabilization strengthen the NuMat, where the basic molecular components remain unchanged ( Sureka et al, 2022 ).…”

“…Only two studies of genome-wide mapping of S/MAR investigate their dynamics during embryonic development or cellular differentiation ( Chunduri et al, 2022 ; Sureka et al, 2022 ). These studies, for the first time, uncovered that these attachment points can be categorized as dynamic or stable (Core-MARs) ( Figure 1 ).…”

“…With the genome-wide study conducted during Drosophila embryonic development ( Sureka et al, 2022 ), it is clear that the functional contribution of S/MARs to gene regulation is driven by both dynamic and stable attachments. The dynamic attachment sites are reversible (likely to be protein factor-induced), functionally derived, closer to or within genes, and differ in various cell types.…”

“…A recent study indicated that TE-derived sequences identify as a significant portion of S/MARs ( Sureka et al, 2022 ). The observation that TEs can act as S/MARs has been reported earlier as well.…”

Polymer Modeling Reveals Interplay between Physical Properties of Chromosomal DNA and the Size and Distribution of Condensin-Based Chromatin Loops

“…Collectively, these chromatin modifications influence its physical attributes, such as compaction and stiffness. Additionally, chromosomal loci can be physically constrained via tethering to external non-chromatin structures such as spindle microtubules, the nuclear lamina in interphase, matrix attachment regions (MARs), and scaffold attachment regions (SARs), or via internal tethering at the base of chromatin loops or by regions of entanglement [1][2][3][4][5]. Involved in a diversity of biological functions, tethering can be permanent and firm, as with the attachments at telomeres and centromeres in yeast [6][7][8][9][10][11].…”