Nuclear Matrix Association: Switching to the Invasive Cytotrophoblast

Abstract

Abnormal trophoblast invasion is associated with the most common and most severe complications of human pregnancy. The biology of invasion, as well as the etiology of abnormal invasion remains poorly understood. The aim of this study was to characterize the transcriptome of the HTR-8/SVneo human cytotrophoblast cell line which displays well characterized invasive and non-invasive behavior, and to correlate the activity of the transcriptome with nuclear matrix attachment and cell phenotype. Comparison of the invasive to non-invasive HTR transcriptomes was unremarkable. In contrast, comparison of the MARs on chromosomes 14-18 revealed an increased number of MARs associated with the invasive phenotype. These attachment areas were more likely to be associated with silent rather than actively transcribed genes. This study supports that view that that nuclear matrix attachment may play an important role in cytotrophoblast invasion by ensuring specific silencing that facilitates invasion.

The sperm nucleus: chromatin, RNA, and the nuclear matrix

“…These have including the development of unique genomic array system capable of simultaneously and specifically assaying the single copy transgenic human protamine domain in addition to the endogenous locus (Johnson G.D. 2010). Utilizing these methods similar studies have been reported in varied somatic cell-types (Linnemann et al 2007, Linnemann & Krawetz 2009, Linnemann et al 2009, Drennan et al 2010). Preliminary analysis of the human sperm nuclear matrix from four donors has yielded intriguing results (Figure 2A and B).…”

“…The strong fluorescent signal corresponds to chromatin at the bases of the DNA loop domains which remain associated with the nuclear matrix (Kramer & Krawetz 1996). Similar extraction protocols are commonly used with somatic cells; though due to the absence of disulfide bonds reducing agents are not required (Berezney & Coffey 1977, Linnemann et al 2009, Drennan et al 2010). …”

“…This proteinaceous network present in most cells functionally organizes the genome by binding discreet regions of DNA at sequences termed Scaffold/Matrix Attachment Regions (S/MARs). S/MAR binding partitions the genome into cell-type specific loop domains which range in size from 30 – 110 kb in somatic cells (Vogelstein et al 1980, Linnemann et al 2009, Drennan et al 2010) and 20 – 50 kb in sperm (Ward et al 1989, Barone et al 1994, Nadel et al 1995). Nucleosome-bound DNA maintained in mature sperm has been proposed to mark sites of nuclear matrix attachment in these cells.…”

The nuclear form of glutathione peroxidase 4 colocalizes and directly interacts with protamines in the nuclear matrix during mouse sperm chromatin assembly

“…Of note, we also observed that nGPx4 has a specific subnuclear distribution in the nuclear matrix of haploid male germ cells, from round spermatids to cauda epididymal sperm 12 . Although the reason for this localization remains unclear, it is indeed intriguing, because nuclear matrix binds chromatin at sequence-specific regions of attachment, the so-called matrix attachment regions (MARs), which exhibit a variety of functions, including chromosome organization into discrete domains and chromatin potentiation 14 , 15 . As an example, the sperm genome displays two haploid-specific MARs flanking the protamine domain, a DNA region containing a cluster of three genes encoding the proteins responsible for DNA packaging protamine 1, protamine 2, and transition protein 2 16 , 17 .…”

DNA polymorphism and epigenetic marks modulate the affinity of a scaffold/matrix attachment region to the nuclear matrix

“…S/MARs anchor chromatin onto the NM, thereby organizing the genomic DNA into topologically distinct loop domains that are important for the regulation of replication and transcription. 2 Despite numerous genomic studies, [3][4][5][6][7] no consensus S/MAR sequence has been identified so far. 8 S/MARs can be both A/T 9 or G/C rich.…”