LAP2 ζ binds BAF and suppresses LAP2 β-mediated transcriptional repression

• Published in: European journal of cell biology 2008-05, Vol.87 (5), p.267-278
• Main Authors: Shaklai, Sigal, Somech, Raz, Gal-Yam, Einav Nili, Deshet-Unger, Naamit, Moshitch-Moshkovitz, Sharon, Hirschberg, Koret, Amariglio, Ninette, Simon, Amos J., Rechavi, Gideon
• Format: Article
• Language: English
• Subjects: BAF; Chromatin; Epigenetics; Histone modification; LAP2; LEM; Nuclear envelope; Nuclear lamina; PIC; Transcription
• ISSN: 0171-9335; 1618-1298
• DOI: 10.1016/j.ejcb.2008.01.014

Proteins of the nuclear envelope have been implicated as participating in gene silencing. BAF, a DNA- and LEM domain-binding protein, has been suggested to link chromatin to the nuclear envelope. We have previously shown that LAP2 β, a LEM-domain inner nuclear membrane protein, represses transcription through binding to HDAC3 and induction of histone H4 deacetylation. We now show that LAP2 ζ, the smallest LAP2 family member, is also involved in regulation of transcription. We show that similar to other LEM-domain proteins LAP2 ζ interacts with BAF. LAP2 ζ-YFP and BAF co-localize in the cytoplasm, and overexpression of LAP2 ζ leads to reduction of nucleoplasmic BAF. Mutations in the LAP2 ζ-YFP LEM domain decrease its interaction with BAF retaining the nucleo-cytoplasmic distribution of BAF. Co-expression of LAP2 β and LAP2 ζ results in inhibition of LAP2 β-induced gene silencing while overexpression of LAP2 ζ alone leads to a small increase in transcriptional activity of various transcription factors. Our results suggest that LAP2 ζ is a transcriptional regulator acting predominantly to inhibit LAP2 β-mediated repression. LAP2 ζ may function by decreasing availability of BAF. These findings could have implications in the study of nuclear lamina-associated diseases and BAF-dependent retroviral integration.