Abstract
CTCF is a ubiquitous epigenetic regulator that has been proposed as a master keeper of chromatin organisation. CTCF-like, or BORIS, is thought to antagonise CTCF and has been found in normal testis, ovary and a large variety of tumour cells. The cellular function of BORIS remains intriguing although it might be involved in developmental reprogramming of gene expression patterns. We here unravel the expression of CTCF and BORIS proteins throughout human epidermis. While CTCF is widely distributed within the nucleus, BORIS is confined to the nucleolus and other euchromatin domains. Nascent RNA experiments in primary keratinocytes revealed that endogenous BORIS is present in active transcription sites. Interestingly, BORIS also localises to interphase centrosomes suggesting a role in the cell cycle. Blocking the cell cycle at S phase or mitosis, or causing DNA damage, produced a striking accumulation of BORIS. Consistently, ectopic expression of wild type or GFP- BORIS provoked a higher rate of S phase cells as well as genomic instability by mitosis failure. Furthermore, down-regulation of endogenous BORIS by specific shRNAs inhibited both RNA transcription and cell cycle progression. The results altogether suggest a role for BORIS in coordinating S phase events with mitosis.
Highlights
CTCF is a Zinc finger DNA binding protein initially identified as a transcriptional regulator [1] and later established as a chromatin insulator binding protein [2]
CTCF and BORIS in Human Epidermis We have presented a strong body of evidence for the expression of CTCF and BORIS proteins in human epidermis
The lower level of CTCF protein in differentiating layers of epidermis is consistent with its function in limiting cell growth, since keratinocyte differentiation involves cell size and cell mass increase [27,28,54]
Summary
CTCF is a Zinc finger DNA binding protein initially identified as a transcriptional regulator [1] and later established as a chromatin insulator binding protein [2]. CTCF has attracted much attention in the last years since it has been associated with heritable genomic imprinting [2,3] and it has been proposed as a master keeper of global chromatin structure [4,5]. The BORIS protein (663 aminoacids) exhibits high homology with CTCF in the central domain containing 11 Zinc-Finger elements, where every amino acid relevant to DNA binding is exactly the same. CTCF and BORIS might bind to the same DNA target sequences. The flanking Nand C- terminal regions show very little sequence homology between of BORIS and CTCF, implying that they may recruit different associated cofactors [11,12,13]
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