Human CRAMP1 specifically promotes the expression of histone H1 genes

Proper histone gene expression is critical for cell viability and maintenance of genomic integrity. Multiple histone genes are organized into three genomic loci that encode replication-coupled core and linker histones. Histone gene expression and transcript processing are orchestrated in the histone locus body (HLB) within the nucleus. Here, we identify human CRAMP1 as a selective regulator of the linker histone H1 expression. Human CRAMP1 is recruited to the HLB in RPE1^hTERT cells. Immunoprecipitation combined with mass spectrometry shows CRAMP1 physically associates with the HLB component GON4L (also known as YARP). We demonstrate that the PAH domains of GON4L interact with CRAMP1. CRAMP1 disruption results in reduced histone H1 mRNA expression and histone H1 protein levels, with no significant changes in core histone gene expression. CRAMP1 occupies the promoters of actively expressed replication-coupled linker histone genes that reside within the histone locus body and replication-independent histone H1 loci, which reside in a region of the genome without other histone genes. Together, these data identify CRAMP1 as a novel and selective regulator of histone H1 gene expression.