Abstract
BackgroundThe human CGGBP1 binds to GC-rich regions and interspersed repeats, maintains homeostasis of stochastic cytosine methylation and determines DNA-binding of CTCF. Interdependence between regulation of cytosine methylation and CTCF occupancy by CGGBP1 remains unknown.ResultsBy analyzing methylated DNA-sequencing data obtained from CGGBP1-depleted cells, we report that some transcription factor-binding sites, including CTCF, resist stochastic changes in cytosine methylation. By analysing CTCF-binding sites we show that cytosine methylation changes at CTCF motifs caused by CGGBP1 depletion resist stochastic changes. These CTCF-binding sites are positioned at locations where the spread of cytosine methylation in cis depends on the levels of CGGBP1.ConclusionOur findings suggest that CTCF occupancy and functions are determined by CGGBP1-regulated cytosine methylation patterns.
Highlights
The human CGGBP1 binds to GC-rich regions and interspersed repeats, maintains homeostasis of stochastic cytosine methylation and determines DNA-binding of CTCF
(See figure on previous page.) Fig. 1 Stochastic cytosine methylation patterns are selectively dependent on CGGBP1 depletiona A schematic representation of the two main methods used to quantify and compare Methyl(cytosine) DNA immunoprecipitation (MeDIP) signals from Non-targeting shRNA or siRNA sample (CT) and CGGBP1-targeting shRNA or siRNA sample (KD)
Unexpected levels of allelic imbalance in MeDIP DNA upon CGGBP1 depletion To find out the contribution of allelic imbalances towards stochasticity of methylation changes observed upon CGGBP1 depletion, we studied the proportions of alleles represented in MeDIP data separately for HEK293T and GM02639
Summary
The human CGGBP1 binds to GC-rich regions and interspersed repeats, maintains homeostasis of stochastic cytosine methylation and determines DNA-binding of CTCF. CTCF is a chromatin architectural protein with a broad repertoire of functions [1]. It is regarded as a principal regulator of higher-order chromatin structure. Of the eleven Zn fingers in CTCF, one ZN7 interacts with cytosine in a methylationsensitive manner [7]. This inhibition of CTCF-DNA binding and its function by motif methylation is a mechanism that regulates site-specific insulator activities of CTCF [8,9,10,11,12]. While a lot of research has addressed the functions and regulatory
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