LILRB1 Intron 1 Has a Polymorphic Regulatory Region That Enhances Transcription in NK Cells and Recruits YY1

Area of Science:

• Immunology
• Molecular Biology
• Genetics

Background:

• Leukocyte Immunoglobulin Like Receptor B1 (LILRB1) is a polymorphic immune receptor implicated in viral and autoimmune diseases.
• LILRB1 expression varies among individuals and is regulated differently in lymphoid and myeloid cells via distinct promoters.
• The precise mechanisms controlling LILRB1 transcription in human Natural Killer (NK) cells remain largely unelucidated.

Purpose of the Study:

• To identify regulatory elements controlling LILRB1 gene transcription in human NK cells.
• To investigate the role of a specific intronic region in LILRB1 gene regulation.
• To determine the involvement of transcription factor YY1 in LILRB1 expression.

Main Methods:

• Chromatin immunoprecipitation-loop assays utilizing anti-YY1 antibody.
• CRISPR-mediated deletion of a 3-kb intronic region in NKL cells.
• Analysis of LILRB1 gene expression following genetic manipulation.

Main Results:

• A polymorphic 3-kb region within LILRB1 intron 1 was identified as an active enhancer in human lymphoid cells but not monocytes.
• This intronic enhancer region contains multiple binding sites for the transcription factor YY1.
• Deletion of this 3-kb region using CRISPR technology resulted in decreased LILRB1 expression in human NKL cells.

Conclusions:

• The intronic enhancer region binds YY1, suggesting a crucial role for this transcription factor in regulating LILRB1.
• YY1 likely acts as a scaffold, facilitating enhancer function to control LILRB1 gene transcription in human NK cells.
• These findings provide novel insights into the epigenetic regulation of LILRB1 in immune cells.