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The amniote-conserved DNA-binding domain of CGGBP1 restricts cytosine methylation of transcription factor binding sites in proximal promoters to regulate gene expression

ABSTRACT: Truncated forms of CGGBP1 with (N-term) or without (C-term) the DNA-binding domain (DBD) have been used to to assay global gene expression. HEK293T cells with endogenous CGGBP1 knocked down were used to over-express truncated forms of CGGBP1 followed by RNA extraction and one-coloured global gene expression analysis. The data suggests that while the C-term of CGGBP1 is the major repressor of transcription, just the N-term containing the DBD fails to achieve so. Proximal promoters of CGGBP1-repressed genes, although significantly GC-poor, contain GC-rich transcription factor binding motifs and exhibit base compositions indicative of low C-T transition rates due to targeted prevention of cytosine methylation. Our findings suggest that CGGBP1 protects transcription factor binding sites (TFBS) from cytosine methylation-associated loss and thereby regulates gene expression. By analysing orthologous promoter sequences, we show that protection from cytosine methylation is a function of CGGBP1 progressively acquired during vertebrate evolution.

ORGANISM(S): Homo sapiens

PROVIDER: GSE269654 | GEO | 2024/11/17

REPOSITORIES: GEO

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The amniote-conserved DNA-binding domain of CGGBP1 restricts cytosine methylation of transcription factor binding sites in proximal promoters to regulate gene expression (HTS)

Project description:Truncated forms of CGGBP1 with (N-term) or without (C-term) the DNA-binding domain (DBD) have been used to to assay global cytosine methylation. HEK293T cells with endogenous CGGBP1 knocked down were used to over-express truncated forms of CGGBP1 followed by MeDIP-Seq analysis. Genome-wide analyses of cytosine methylation and binding of CGGBP1 DBD show that CGGBP1 restricts cytosine methylation in a manner that depends on its DBD and its DNA-binding. Our findings suggest that CGGBP1 protects transcription factor binding sites (TFBS) from cytosine methylation-associated loss. A superimposition of our results and evolution of CGGBP1 suggests that mitigation of cytosine methylation is majorly achieved by its N-terminal DBD. Our results position CGGBP1 DNA-binding as a major evolutionarily acquired mechanism through which it keeps cytosine methylation under check and regulates TFBS retention.

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