Novel CTCF binding at a site in exon1A of BCL6 is associated with active histone marks and a transcriptionally active locus. Novel CTCF binding at a site in exon1A of BCL6 is associated with active histone marks and a transcriptionally active locus. Batlle-López A, Cortiguera MG, Rosa-Garrido M, Blanco R, Del Cerro E, Torrano V, Wagner SD, Delgado MD. Oncogene. 2015 Jan 8;34(2):246-56. doi: 10.1038/onc.2013.535. 2015-01-07T23:00:00Z<div style="text-align:justify;"></div><p style="text-align:justify;"><span class="ms-rteThemeFontFace-1 ms-rteFontSize-2"><span class="ms-rteThemeForeColor-2-5 ms-rteThemeFontFace-1 ms-rteFontSize-2" style="font-weight:bold;">Abstract</span><br></span></p><div style="color:#000000;font-family:arial, helvetica, clean, sans-serif;text-align:justify;"><p style="margin-bottom:0.5em;font-size:1.04em;"><span class="ms-rteThemeFontFace-1 ms-rteFontSize-2">BCL6 is a zinc-finger transcriptional repressor, which is highly expressed in germinal centre B-cells and is essential for germinal centre formation and T-dependent antibody responses. Constitutive BCL6 expression is sufficient to produce lymphomas in mice. Deregulated expression of BCL6 due to chromosomal rearrangements, mutations of a negative autoregulatory site in the BCL6 promoter region and aberrant post-translational modifications have been detected in a number of human lymphomas. Tight lineage and temporal regulation of BCL6 is, therefore, required for normal immunity, and abnormal regulation occurs in lymphomas. CCCTC-binding factor (CTCF) is a multi-functional chromatin regulator, which has recently been shown to bind in a methylation-sensitive manner to sites within the BCL6 first intron. We demonstrate a novel CTCF-binding site in BCL6 exon1A within a potential CpG island, which is unmethylated both in cell lines and in primary lymphoma samples. CTCF binding, which was found in BCL6-expressing cell lines, correlated with the presence of histone variant H2A.Z and active histone marks, suggesting that CTCF induces chromatin modification at a transcriptionally active BCL6 locus. CTCF binding to exon1A was required to maintain BCL6 expression in germinal centre cells by avoiding BCL6-negative autoregulation. Silencing of CTCF in BCL6-expressing cells reduced BCL6 mRNA and protein expression, which is sufficient to induce B-cell terminal differentiation toward plasma cells. Moreover, lack of CTCF binding to exon1A shifts the BCL6 local chromatin from an active to a repressive state. This work demonstrates that, in contexts in which BCL6 is expressed, CTCF binding to BCL6 exon1A associates with epigenetic modifications indicative of transcriptionally open chromatin.</span></p></div><p>​<span style="color:#474f51;font-family:"yanone kaffeesatz";font-size:18px;background-color:#ffffff;">[</span><a href="" style="color:#ed391b;margin:0px;padding:0px;border:0px;font-stretch:inherit;font-size:18px;line-height:inherit;font-family:"yanone kaffeesatz";vertical-align:baseline;background-color:#ffffff;">PubMed</a><span style="color:#474f51;font-family:"yanone kaffeesatz";font-size:18px;background-color:#ffffff;">]</span><br></p>109