Mbd1 is recruited to both methylated and nonmethylated CpGs via distinct DNA binding domains

MBD1 is a vertebrate methyl-CpG binding domain protein (MBD) that can bring about repression of methylated promoter DNA sequences. Like other MBD proteins, MBD1 localizes to nuclear foci that in mice are rich in methyl-CpG. In methyl-CpG-deficient mouse cells, however, Mbd1 remains localized to heterochromatic foci whereas other MBD proteins become dispersed in the nucleus. We find that Mbd1a, a major mouse isoform, contains a CXXC domain (CXXC-3) that binds specifically to nonmethylated CpG, suggesting an explanation for methylation-independent localization. Transfection studies demonstrate that the CXXC-3 domain indeed targets nonmethylated CpG sites in vivo. Repression of nonmethylated reporter genes depends on the CXXC-3 domain, whereas repression of methylated reporters requires the MBD. Our findings indicate that MBD1 can interpret the CpG dinucleotide as a repressive signal in vivo regardless of its methylation status

M.M. Thomas: Theological Signposts for the Emergence of Dalit Theology

Dalit Christian Theology emerged as a counter theological movement in India in the 1980s. As a theology ‘of the Dalits, by the Dalits, for the Dalits’, Dalit Christian theology sought to counter prevalent trends in Indian Christian theology which had proved inadequate to reflect the actual experience of the majority of Christians in India. The emergence of Dalit Christian theology as a contextual liberation theology thus reflects a polarising shift in theological discourse within India. This thesis argues, however, that the theology of M.M. Thomas, a leading non-Dalit Indian Christian theologian of the twentieth Century, offered significant theological signposts for the emergence and development of Dalit Christian theology. While it is clear that he did not, nor could not, construct a Dalit theology, this thesis argues that Thomas’s theological reflections in the midst of a rapidly changing and pluralistic religio-secular Indian context brought to the fore of theological debate essential questions relating to the concept of salvation, humanisation and justice relevant to the emergence of Dalit Christian theology. Seeking to relate Christology to the Indian context dynamically, M.M. Thomas sought a theology which could be ‘challengingly relevant’ to the people of India in the post-Independent search for a just and equal society. In order to substantiate the thesis, this study examines the reflections of two first generation Dalit Christian theologians, Bishop M. Azariah and Bishop V. Devasahayam. From within a framework of methodological exclusivism, both theologians appear to reject the theological contribution of M.M. Thomas, regarding him an Indian Christian theologian with little relevance to the Dalit theological quest. Closer textual examination, however, reveals that the theological contribution of M.M. Thomas is discernable within emerging Dalit theological discourse. This thesis further investigates the relevance of M.M. Thomas’s theological contribution for Dalit Christian theology today through the critical assessment of twelve second generation Dalit theologians studying at United Theological College, Bangalore. These voices assess the rise of Dalit Christian theology, and examine the relevance of Thomas’s thoughts for contemporary Dalit discourse

Molecular biology - Methylation talk between histones and DNA

The addition of methyl groups to DNA or histones is a way to directly or indirectly silence gene expression. Although the two events are conceivably connected, they have always been studied separately. In his Perspective, Bird explores the exciting notion (supported by data published elsewhere) that the two events are irrevocably linked, that is, DNA methylation depends on histone methylatio

Engineering a high-affinity methyl-CpG-binding protein

Core members of the MBD protein family (MeCP2, MBD1, MBD2 and MBD4) share a methyl-CpG-binding domain that has a specific affinity for methylated CpG sites in double-stranded DNA. By multimerizing the MDB domain of Mbd1, we engineered a poly-MBD protein that displays methyl-CpG-specific binding in vitro with a dissociation constant that is >50-fold higher than that of a monomeric MBD. Poly-MBD proteins also localize to methylated foci in cells and can deliver a functional domain to reporter constructs in vivo. We propose that poly-MBD proteins are sensitive reagents for the detection of DNA methylation levels in isolated native DNA and for cytological detection of chromosomal CpG methylatio

Engineering a high-affinity methyl-CpG-binding protein

Core members of the MBD protein family (MeCP2, MBD1, MBD2 and MBD4) share a methyl-CpG-binding domain that has a specific affinity for methylated CpG sites in double-stranded DNA. By multimerizing the MDB domain of Mbd1, we engineered a poly-MBD protein that displays methyl-CpG-specific binding in vitro with a dissociation constant that is >50-fold higher than that of a monomeric MBD. Poly-MBD proteins also localize to methylated foci in cells and can deliver a functional domain to reporter constructs in vivo. We propose that poly-MBD proteins are sensitive reagents for the detection of DNA methylation levels in isolated native DNA and for cytological detection of chromosomal CpG methylation

MeCP2 Repression Goes Nonglobal

Methylation of CpG islands in gene promoters results in silencing of those genes. Mutation of a methyl-CpG binding domain protein called MeCP2 that contributes to the maintenance of methylation-mediated gene silencing is associated with a severe neurological disease called Rett syndrome. As Klose and Bird report in their Perspective, new work published here (Chen et al., Martinowich et al.) and elsewhere demonstrates that MeCP2 normally represses the expression of two genes-BDNF in rat and Hairy2a in frog-that are crucial for normal development of the nervous system

Absence of genome-wide changes in DNA methylation during development of the zebrafish

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