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      Prediction of Gene Expression Patterns With Generalized Linear Regression Model

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          Abstract

          Cell reprogramming has played important roles in medical science, such as tissue repair, organ reconstruction, disease treatment, new drug development, and new species breeding. Oct4, a core pluripotency factor, has especially played a key role in somatic cell reprogramming through transcriptional control and affects the expression level of genes by its combination intensity. However, the quantitative relationship between Oct4 combination intensity and target gene expression is still not clear. Therefore, firstly, a generalized linear regression method was constructed to predict gene expression values in promoter regions affected by Oct4 combination intensity. Training data, including Oct4 combination intensity and target gene expression, were from promoter regions of genes with different cell development stages. Additionally, the quantitative relationship between gene expression and Oct4 combination intensity was analyzed with the proposed model. Then, the quantitative relationship between gene expression and Oct4 combination intensity at each stage of cell development was classified into high and low levels. Experimental analysis showed that the combination height of Oct4-inhibited gene expression decremented by a temporal exponential value, whereas the combination width of Oct4-promoted gene expression incremented by a temporal logarithmic value. Experimental results showed that the proposed method can achieve goodness of fit with high confidence.

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          Most cited references47

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          Reprogramming of human somatic cells to pluripotency with defined factors.

          Pluripotency pertains to the cells of early embryos that can generate all of the tissues in the organism. Embryonic stem cells are embryo-derived cell lines that retain pluripotency and represent invaluable tools for research into the mechanisms of tissue formation. Recently, murine fibroblasts have been reprogrammed directly to pluripotency by ectopic expression of four transcription factors (Oct4, Sox2, Klf4 and Myc) to yield induced pluripotent stem (iPS) cells. Using these same factors, we have derived iPS cells from fetal, neonatal and adult human primary cells, including dermal fibroblasts isolated from a skin biopsy of a healthy research subject. Human iPS cells resemble embryonic stem cells in morphology and gene expression and in the capacity to form teratomas in immune-deficient mice. These data demonstrate that defined factors can reprogramme human cells to pluripotency, and establish a method whereby patient-specific cells might be established in culture.
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            In vitro reprogramming of fibroblasts into a pluripotent ES-cell-like state.

            Nuclear transplantation can reprogramme a somatic genome back into an embryonic epigenetic state, and the reprogrammed nucleus can create a cloned animal or produce pluripotent embryonic stem cells. One potential use of the nuclear cloning approach is the derivation of 'customized' embryonic stem (ES) cells for patient-specific cell treatment, but technical and ethical considerations impede the therapeutic application of this technology. Reprogramming of fibroblasts to a pluripotent state can be induced in vitro through ectopic expression of the four transcription factors Oct4 (also called Oct3/4 or Pou5f1), Sox2, c-Myc and Klf4. Here we show that DNA methylation, gene expression and chromatin state of such induced reprogrammed stem cells are similar to those of ES cells. Notably, the cells-derived from mouse fibroblasts-can form viable chimaeras, can contribute to the germ line and can generate live late-term embryos when injected into tetraploid blastocysts. Our results show that the biological potency and epigenetic state of in-vitro-reprogrammed induced pluripotent stem cells are indistinguishable from those of ES cells.
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              RNA-mediated epigenetic regulation of gene expression.

              Diverse classes of RNA, ranging from small to long non-coding RNAs, have emerged as key regulators of gene expression, genome stability and defence against foreign genetic elements. Small RNAs modify chromatin structure and silence transcription by guiding Argonaute-containing complexes to complementary nascent RNA scaffolds and then mediating the recruitment of histone and DNA methyltransferases. In addition, recent advances suggest that chromatin-associated long non-coding RNA scaffolds also recruit chromatin-modifying complexes independently of small RNAs. These co-transcriptional silencing mechanisms form powerful RNA surveillance systems that detect and silence inappropriate transcription events, and provide a memory of these events via self-reinforcing epigenetic loops.
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                Author and article information

                Contributors
                Journal
                Front Genet
                Front Genet
                Front. Genet.
                Frontiers in Genetics
                Frontiers Media S.A.
                1664-8021
                04 March 2019
                2019
                : 10
                : 120
                Affiliations
                [1] 1College of Information Science and Engineering, Hunan Normal University , Changsha, China
                [2] 2College of Computer Science, Inner Mongolia University , Hohhot, China
                [3] 3College of Life Sciences, Inner Mongolia University , Hohhot, China
                [4] 4The State Key Laboratory of Reproductive Regulation and Breeding of Grassland Livestock, Inner Mongolia University , Hohhot, China
                Author notes

                Edited by: Arun Kumar Sangaiah, VIT University, India

                Reviewed by: Yu-Dong Zhang, University of Leicester, United Kingdom; Jose Tenreiro Machado, Instituto Superior de Engenharia do Porto (ISEP), Portugal; Jianzhong Su, Wenzhou Medical University, China

                *Correspondence: Shuai Liu cs.liu.shuai@ 123456gmail.com

                This article was submitted to Bioinformatics and Computational Biology, a section of the journal Frontiers in Genetics

                Article
                10.3389/fgene.2019.00120
                6409355
                30886626
                e6b12862-926f-4c16-9f48-781d80a5e9eb
                Copyright © 2019 Liu, Lu, Li and Zuo.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 06 November 2018
                : 04 February 2019
                Page count
                Figures: 5, Tables: 8, Equations: 17, References: 55, Pages: 11, Words: 6979
                Funding
                Funded by: National Natural Science Foundation of China 10.13039/501100001809
                Award ID: 61502254
                Categories
                Genetics
                Original Research

                Genetics
                cell reprogramming,oct4,transcription factor binding site (tfbs),combination intensity,generalized linear regression model,gene expression pattern,prediction

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