Fig. 1
Chromatin landscape at the UGT2B17 gene locus in lymphoblastoid cell models and CLL patient cells. A. The UGT2B17 gene locus is comprised of six coding exons and alternative non-coding exons 1d, 1c and 1b. The canonical UGT2B17_v1 and alternative _n1, _n2, _n3, and _n4 transcripts all encode the full length UGT2B17 canonical enzyme. Transcripts _n3 and _n4 include the alternative exon 1b that is extended by 81 nucleotides on the 3’ side (purple hatched box) in transcript _n4. B. Transposase-accessible chromatin regions (ATAC-seq) at the UGT2B17 gene locus across a cohort of CLL patients (n = 88 [16]). The canonical transcript UGT2B17_v1 (RefSeq accession NM_001077.3) and the most recent RefSeq UGT2B17 gene annotation NM_001077.4 encoding UGT2B17_n2 are shown (Annotation Release NCBI Homo sapiens 105.20220307). Note that the UGT2B17 locus is on the reverse strand/orientation. C. DNAse hypersensitive sites in ENCODE (V3; n = 125 cell models) and D. Transcription factor-bound chromatin (ChIP-seq clusters (n = 161 factors) from ENCODE with Factorbook Motifs) at the UGT2B17 5’UTR gene locus detected in lymphoblastoid cell models; Data in panels B-D was obtained from the UCSC browser (http://genome.ucsc.edu) [17] version GRCh37/hg19 accessed in January 2023. The position of exon 1b, not included in the current public gene annotation, is indicated by a purple box. E. Relative expression of total UGT2B17, UGT2B17_n2 and UGT2B17_n4 transcripts assessed by RT-qPCR in lymphoblastoid and B-CLL cell models previously studied to demonstrate UGT2B17 oncogenic functions [2, 3, 5, 18], and in B-cells from healthy individuals and CLL patients. Note that CLL patients expressing high levels of UGT2B17 (UGT2B17HI) were screened. F. Chromatin features at the UGT2B17 gene locus identify P3 and P2 regions as the main transcriptional regulatory regions in CLL and lymphoblastoid cell models whereas the canonical UGT2B17_v1 expression is undetected [2]. Coordinates are relative to the UGT2B17 translation start site (+ 1) according to the data on the UCSC browser (GRCh37/hg19). The features of the genomic DNA sequence at the UGT2B17 locus are detailed in Supplementary data 1, Supplementary file 1